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Catalog No. Product Name Information Product Use Citations Product Validations
S1013 Bortezomib (PS-341) Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.
J Cell Biol, 2022, 221(1)e202103033
Nature, 2021, 10.1038/s41586-020-03118-2
Nat Cell Biol, 2021, 10.1038/s41556-021-00766-y
S1092 KU-55933 (ATM Kinase Inhibitor) KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy.
Nat Genet, 2021, 10.1038/s41588-021-00893-0
Cancer Cell, 2021, S1535-6108(20)30658-9
Sci Transl Med, 2021, 13(622):eabb5445
S1102 U0126-EtOH U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. U0126 inhibits autophagy and mitophagy with antiviral activity.
J Am Chem Soc, 2021, 10.1021/jacs.1c05386
Sci Adv, 2021, 7(36):eabi9787
Theranostics, 2021, 11(3):996-1015
S1105 LY294002 LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
Biomed Pharmacother, 2022, 145:112437
Immunity, 2021, S1074-7613(21)00069-8
Immunity, 2021, S1074-7613(21)00403-9
S1109 BI 2536 BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
Nat Commun, 2021, 12(1):5356
Proc Natl Acad Sci U S A, 2021, 118(34)e2108145118
S1113 GSK690693 GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. GSK690693 also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively. GSK690693 affects Unc-51-like autophagy activating kinase 1 (ULK1) activity, robustly inhibits STING-dependent IRF3 activation. Phase 1.
Oncogene, 2021, 10.1038/s41388-021-01932-0
Breast Cancer Res, 2021, 23(1):81
Cancer Discov, 2021, candisc.1265.2020
S1150 Paclitaxel (NSC 125973) Paclitaxel (NSC 125973, PTX, Taxol, Onxal, Abraxane) is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancer Cell, 2021, S1535-6108(20)30658-9
S1346 Heparin sodium Heparin sodium, a sulfated polysaccharide belonging to the family of glycosaminoglycans, has numerous important biological activities associated with its interaction with diverse proteins. Heparin is used as an anticoagulant primarily through its interaction with AT III by enhancing AT-IIImediated inhibition of blood coagulation factors, including thrombin and factor Xa. Heparin prevents the induction of autophagy.
J Extracell Vesicles, 2021, 10(8):e12091
Nat Struct Mol Biol, 2021, 10.1038/s41594-020-00537-7
Theranostics, 2021, 11(5):2364-2380
S1413 Bafilomycin A1 (Baf-A1) Bafilomycin A1(Baf-A1) is a vacuolar H+-ATPase inhibitor with IC50 of 0.44 nM. Bafilomycin A1 is found to inhibit autophagy while induces apoptosis.
Adv Sci (Weinh), 2021, e2100779
Mol Cell, 2021, S1097-2765(21)00729-2
ACS Nano, 2021, 10.1021/acsnano.1c06452
S1460 SP600125 SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase AFLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis.
Biomed Pharmacother, 2022, 145:112437
Immunity, 2021, S1074-7613(21)00403-9
Immunity, 2021, S1074-7613(21)00210-7
S1490 Ponatinib (AP24534) Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy.
J Ethnopharmacol, 2022, 283:114667
Acta Neuropathol, 2021, 10.1007/s00401-021-02327-x
Mol Syst Biol, 2021, 17(9):e10426
S1733 Methylprednisolone (NSC-19987) Methylprednisolone (NSC-19987) is a synthetic glucocorticoid receptor agonist, used to achieve prompt suppression of inflammation. Methylprednisolone activates ACE2 and reduces IL-6 levels, thus improves severe or critical COVID-19. Methylprednisolone markedly reduces autophagy and apoptosis.
Drug Test Anal, 2020, 10.1002/dta.2917
Nat Med, 2017, 23(4):424-428
Trop J Pharm Res, 2014, 13 (1): 53-59
S1786 Verteporfin (CL 318952) Verteporfin (CL 318952, Visudyne) is a small molecule that inhibits TEAD–YAP association and YAP-induced liver overgrowth. It is also a potent second-generation photosensitizing agent derived from porphyrin. Verteporfin is an autophagy inhibitor. Verteporfin inhibits cell proliferation and induces apoptosis.
Nature, 2021, 10.1038/s41586-021-04267-8
Cell Res, 2021, 10.1038/s41422-021-00477-x
Nat Commun, 2021, 12(1):3055
S1835 Azithromycin (CP-62993) Azithromycin (CP-62993, XZ-450) is an antibiotic by inhibiting protein synthesis, used for the treatment of bacterial infections.
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Biomolecules, 2020, 10(10)E1395
S2243 Degrasyn (WP1130) Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT). Degrasyn (WP1130) induces apoptosis and blocks autophagy.
Br J Cancer, 2021, 10.1038/s41416-021-01421-x
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Transl Lung Cancer Res, 2021, 10(10):3995-4011
S2704 LY2109761 LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2. LY2109761 blocks autophagy and induces apoptosis.
Nat Commun, 2021, 12(1):2102
Nucleic Acids Res, 2021, 49(22):12855-12869
Cell Rep, 2021, 34(12):108882
S2758 Wortmannin (KY 12420) Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Adv Sci (Weinh), 2021, e2004303
J Extracell Vesicles, 2021, 10(8):e12091
J Am Chem Soc, 2021, 10.1021/jacs.1c05386
S2767 3-Methyladenine (3-MA) 3-Methyladenine (3-MA, NSC 66389) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation. 3-Methyladenine (3-MA) is successfully used to suppress mitophagy. Solutions of 3-MA are best fresh-prepared by heating.
Bone, 2022, 154:116262
Cell Host Microbe, 2021, S1931-3128(21)00192-X
Nat Commun, 2021, 12(1):4794
S2775 Nocodazole (R17934) Nocodazole (R17934, Oncodazole, NSC238159) is a rapidly-reversible inhibitor of microtubule polymerization, also inhibits Abl, Abl(E255K) and Abl(T315I) with IC50 of 0.21 μM, 0.53 μM and 0.64 μM in cell-free assays, respectively. Nocodazole induces apoptosis.
Cancer Cell, 2021, S1535-6108(21)00383-4
Mol Cell, 2021, S1097-2765(21)00736-X
Nat Commun, 2021, 12(1):5977
S2930 Pifithrin-μ Pifithrin-μ (NSC 303580, PFTμ, 2-Phenylethynesulfonamide) is a specific p53 inhibitor by reducing its affinity to Bcl-xL and Bcl-2, and also inhibits HSP70 function and autophagy.
Shock, 2021, 55(1):74-82
Radiat Res, 2020, 193(2):119-129
Clin Transl Med, 2020, 10.1002/ctm2.41
S3042 Purmorphamine Purmorphamine (Shh Signaling Antagonist VI), which directly binds and activates Smoothened, blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM in HEK293T cell and also is an inducer of osteoblast differentiation with EC50 of 1 μM. Purmorphamine can reduce both basal and induced autophagy.
Cancer Cell, 2021, 39(3):407-422.e13
Front Cell Dev Biol, 2021, 9:679806
Can J Physiol Pharmacol, 2021, 10.1139/cjpp-2020-0588
S3233 Emetine hydrochloride Emetine hydrochloride (NSC 33669), a principal alkaloid extracted from the root of ipecac clinically used as an emetic and antiprotozoal drug, reduces HIFs (hypoxia-inducible factors; HIF-1α and HIF-2α), PDK1, RhoA, Rho-kinases (ROCK1 and ROCK2) and BRD4. Emetine hydrochloride inhibits cellular autophagy and has anti-malarial, anti-viral, anti-bacterial and anti-amoebic effect.
S3592New 4-Phenylbutyric acid (4-PBA) 4-Phenylbutyric acid (4-PBA, Benzenebutyric acid) is a histone deacetylase (HDAC) inhibitor and a key epigenetic inducer of anti-HCV hepatic hepcidin. 4-Phenylbutyric acid inhibits LPS-induced inflammation through regulating endoplasmic-reticulum (ER) stress and autophagy in acute lung injury models.
Toxicol In Vitro, 2021, 77:105249
Nan Fang Yi Ke Da Xue Xue Bao, 2021, 41(5):702-709
Part Fibre Toxicol, 2020, 17(1):50
S3758 Sinomenine hydrochloride Sinomenine (SN, Cucoline, Kukoline, Sabianine A), extracted from the Chinese medicinal plant, sinomenium acutum, is a potent anti-inflammatory and neuroprotective agent.
Cancer Manag Res, 2021, 13:1189-1204
Bioorg Med Chem, 2020, 31:115986
S4157 Chloroquine diphosphate Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator. Chloroquine is also an inhibitor of toll-like receptors (TLRs).
Bone, 2022, 154:116262
Cancer Cell, 2021, S1535-6108(21)00659-0
Gut, 2021, 70(5):890-899
S4430 Hydroxychloroquine Sulfate (NSC 4375) Hydroxychloroquine Sulfate (NSC 4375, HCQ) is an antimalarial agent used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune, inflammatory and dermatologic conditions. Also acts as an inhibitor of autophagy and toll-like receptor (TLR) 7/9.
Autophagy, 2021, 1-14
EMBO Mol Med, 2021, 13(9):e13193
Cell Rep, 2021, 35(1):108940
S4484New Trametinib DMSO solvate Trametinib (GSK1120212, JTP-74057, Mekinist) DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis.
S4643New KB-R7943 mesylate KB-R7943 mesylate is a widely used inhibitor of the reverse Na+/Ca2+ exchanger (NCX(rev)) with IC50 of 5.7 μM. KB-R7943 mesylate promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux.
S4895New Nilotinib hydrochloride monohydrate Nilotinib (AMN-107, Tasigna) hydrochloride monohydrate is a selective and orally bioavailable inhibitor of Bcr-Abl with IC50 < 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
EMBO Mol Med, 2021, e11814
Mol Metab, 2021, 55:101410
Cancers (Basel), 2021, 13(21)5543
S5190New Crizotinib hydrochloride Crizotinib (PF-02341066) hydrochloride (Xalkori) inhibits tyrosine phosphorylation of c-Met and nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) with IC50 of of 11 nM and 24 nM in cell-based assays, respectively. Crizotinib hydrochloride is also a potent ROS1 inhibitor with Ki less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Nature, 2021, 600(7888):319-323
Nat Commun, 2021, 12(1):5006
Cancer Res, 2021, 81(23):5935-5947
S5920 CA-5f CA-5f is a potent late-stage macroautophagy/autophagy inhibitor via inhibiting autophagosome-lysosome fusion.
J Virol, 2021, JVI0155021
S5971New Pemetrexed Pemetrexed (LY231514, Alimta) is a novel antifolate and antimetabolite for thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT) with Ki of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.
J Exp Clin Cancer Res, 2021, 40(1):344
Br J Cancer, 2021, 10.1038/s41416-021-01441-7
Front Oncol, 2021, 11:711043
S6078New ICCB-19 hydrochloride ICCB-19 hydrochloride is an inhibitor of TNFRSF1A Associated Via Death Domain (TRADD) with IC50 of 1.12 μM and 2.01 μM for protecting Velcade-induced apoptosis in Jurkat cells and protecting RDA in MEFs, respectively. ICCB-19 indirectly inhibits Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). ICCB-19 effectively induces autophagy.
S6471 Lucanthone Lucanthone is a novel autophagic inhibitor and also an orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1.
S6716 NSC 185058 NSC185058 inhibits ATG4B, the lipidation of LC3B, and autophagy without affecting the MTOR or PtdIns3K pathways.
S6912 Vacuolin-1 Vacuolin-1 is a potent and cell-permeable inhibitor that blocks the Ca(2+)-dependent exocytosis of lysosomes and prevents the release of lysosomal content without affecting the process of resealing. Vacuolin-1 is also a potent and selective PIKfyve inhibitor, and inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition.
S6999New Chloroquine (NSC-187208) Chloroquine (NSC-187208, Aralen, CHQ, CQ) is an antimalarial drug and autophagy/lysosome inhibitor. Chloroquine also suppresses Toll-like receptor-9 (TLR9) protein expression. Chloroquine is highly effective agianst SARS-CoV-2 (COVID-19) infection with EC50 of 1.13 μM in Vero E6 cells. Chloroquine has anti-HIV-1 activity.
Bone, 2022, 154:116262
Dev Cell, 2021, 56(16):2313-2328.e7
Autophagy, 2021, 10.1080/15548627.2021.1912270
S7033 GSK2656157 GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases apoptosis and inhibits excessive autophagy.
Neurobiol Dis, 2021, 156:105407
Cell Death Dis, 2020, 11(2):125
Sci Rep, 2020, 10(1):9666
S7046 Brefeldin A Brefeldin A is a lactone antibiotic and ATPase inhibitor for protein transport with IC50 of 0.2 μM in HCT 116 cells, induces cancer cell differentiation and apoptosis. It could also improve the HDR(homology-directed repair) efficiency and be an enhancer of CRISPR-mediated HDR. Brefeldin A is also an inhibitor of autophagy and mitophagy.
Nat Cell Biol, 2021, 10.1038/s41556-021-00704-y
Nat Biomed Eng, 2021, 10.1038/s41551-020-00675-9
Cell Rep, 2021, 36(6):109516
S7146 DMH1 DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. DMH1 inhibits autophagy.
Nat Commun, 2021, 12(1):6374
Proc Natl Acad Sci U S A, 2021, 118(29)e2101783118
Cell Rep, 2021, 34(12):108889
S7289 PFK15 PFK15 (PFK-015) is a potent and selective 6-phosphofructo-2-kinase (PFKFB3) inhibitor with IC50 of 207 nM.
Autophagy, 2021, 1-19
Front Immunol, 2021, 12:669456
J Am Heart Assoc, 2021, 10(17):e020231
S7381 Pepstatin A Pepstatin A (Pepstatin) is a potent aspartic protease inhibitor, and also inhibits HIV replication. Pepstatin A is also an inhibitor of cathepsins D and cathepsins E. Pepstatin A inhibits autophagy by suppressing lysosomal proteases.
Pharmacol Res, 2021, S1043-6618(21)00517-X
J Virol, 2021, JVI0155021
Acta Pharmacol Sin, 2021, 10.1038/s41401-021-00768-4
S7423 KN-93 Phosphate KN-93 Phosphate is a potent and specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with Ki of 0.37 μM, no remarkable inhibitory effects on APK, PKC, MLCK or Ca2+-PDE activities. KN-93 attenuates CaMKII-induced autophagy.
Cell Rep, 2021, 35(11):109238
Autophagy, 2021, 1-19
Cell Mol Gastroenterol Hepatol, 2021, S2352-345X(21)00135-1
S7455 Resatorvid (TAK-242) Resatorvid (TAK-242, CLI-095) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling, blocking LPS-induced production of NO, TNF-α and IL-6 in macrophages with IC50 of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy.
FASEB J, 2021, 35(4):e21485
Int J Biol Macromol, 2021, 183:145-157
Front Pharmacol, 2021, 12:626949
S7660 Obeticholic Acid Obeticholic Acid (INT-747, 6-ECDCA, 6-Ethylchenodeoxycholic acid) is a potent and selective farnesoid X receptor (FXR) agonist with EC50 of 99 nM. Obeticholic Acid inhibits autophagy. Phase 3.
Nutrients, 2021, 13(3)940
Proc Natl Acad Sci U S A, 2020, 117(45):28263-28274
Nat Metab, 2020, 2(5):413-431
S7682 SAR405 SAR405 is a low-molecular-mass kinase inhibitor of PIK3C3/Vps34 (KD 1.5 nM) showing high selectivity and not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. SAR405 prevents autophagy and synergizes with MTOR (mechanistic target of rapamycin) inhibition in tumor cells.
Autophagy, 2021, 1-18
Autophagy, 2021, 1-16
Cell Death Dis, 2021, 12(11):1028
S7683 PIK-III PIK-III (VPS34-IN2), which is a selective inhibitor of ​VPS34 enzymatic activity, inhibits autophagy and de novo lipidation of LC3 and leads to the stabilization of autophagy substrates. The IC50 values for VPS34 and PI(3)Kδ are 0.018 μM and 1.2 μM respectively.
Sci Adv, 2021, 7(40):eabj2485
Oxid Med Cell Longev, 2021, 2021:7654143
Nature, 2020, 10.1038/s41586-020-03056-z
S7751 VER155008 VER155008 (C07) is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.
EMBO J, 2021, e106183
Oncogene, 2021, 10.1038/s41388-021-01914-2
Eur J Med Chem, 2021, 220:113452
S7811 MHY1485 MHY1485 is a potent, and cell-permeable mTOR activator, and also potently inhibits autophagy.
Nat Commun, 2021, 12(1):1736
Cell Rep, 2021, 36(5):109490
Cells, 2021, 10(3)558
S7885 SBI-0206965 SBI-0206965 is a highly selective autophagy kinase ULK1 inhibitor with IC50 of 108 nM, about 7-fold selectivity over ULK2. SBI-0206965 inhibits autophagy and enhances apoptosis in human glioblastoma and lung cancer cells.
Mol Cell, 2021, S1097-2765(21)00729-2
Prog Neurobiol, 2021, S0301-0082(21)00137-4
Int J Mol Sci, 2021, 22(4)2046
S7888 Spautin-1 Spautin-1 is a potent and specific autophagy inhibitor, and inhibits the deubiquitinating activity of USP10 and USP13 with IC50 of ∼0.6-0.7 μM. Spautin-1 enhances apoptosis.
J Clin Invest, 2021, 146893
Protein Cell, 2021, 10.1007/s13238-021-00858-3
Autophagy, 2021, 1-19
S7948 MRT67307 HCl MRT67307 is a potent and dual IKKϵ and TBK1 inhibitor with IC50 of 160 and 19 nM, respectively. MRT67307 potently inhibits ULK1 and ULK2 and blocks autophagy.
Cell, 2021, S0092-8674(21)00885-0
Cell Rep, 2020, 33(5):108339
Cancer Discov, 2020, 10(3):382-393
S7949 MRT68921 HCl MRT68921 is a potent and dual autophagy kinase ULK1/2 inhibitor with IC50 of 2.9 nM and 1.1 nM, respectively.
Mol Cell, 2021, 81(9):2013-2030.e9
Cell Rep, 2021, 36(13):109762
Cancer Biol Med, 2021, j.issn.2095-3941.2020.0262
S8037 Necrostatin-1 Necrostatin-1 (Nec-1) is a specific RIP1 (RIPK1) inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM in 293T cells. Necrostatin-1 also blocks IDO and suppresses autophagy and apoptosis.
Cell, 2021, S0092-8674(21)00885-0
Nat Immunol, 2021, 22(9):1107-1117
Adv Sci (Weinh), 2021, 8(10):2004680
S8222 AS1842856 AS1842856 is a cell-permeable inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM. It could directly bind to the active Foxo1, but not the Ser256-phosphorylated form. AS1842856 suppresses autophagy.
J Clin Invest, 2021, 131(1)135937
Int J Mol Sci, 2021, 22(6)3028
Invest Ophthalmol Vis Sci, 2021, 62(3):37
S8274 STO-609 STO-609 is a specific inhibitor of the Ca2+/Calmodulin-dependent protein kinase kinase(CaM-KK) that inhibits the activities of recombinant CaM-KKα and CaM-KKβ isoforms, with Ki values of 80 and 15 ng/ml, respectively, and also inhibits their autophosphorylation activities. STO-609 inhibits AMPKK activity and inhibits autophagy.
Cell Res, 2021, 10.1038/s41422-021-00565-y
Autophagy, 2021, 1-14
Cell Death Dis, 2021, 12(11):972
S8317 3BDO 3BDO, a butyrolactone derivative, could target FKBP1A and activate the mTOR signaling pathway. It inhibits autophagy in HUVECs. 3BDO inhibits oxLDL-induced apoptosis.
Front Oncol, 2021, 11:665420
Mol Med Rep, 2021, 24(2)592
Biomed Res Int, 2020, 2020:4035306
S8369 Lys05 Lys05 is a new lysosomal autophagy inhibitor which potently accumulates within and deacidifies the lysosome of both cells and tumors, resulting in sustained inhibition of autophagy and tumor growth.
Blood Cancer J, 2021, 11(6):111
Surgery, 2021, S0039-6060(21)00795-9
Environ Toxicol, 2021, 10.1002/tox.23355
S8527 ROC-325 ROC-325 is an orally available novel inhibitor of lysosomal-mediated autophagy which diminishes AML cell viability with the IC50 range of 0.7-2.2 μM.
S8576 EAD1 EAD1 is a potent autophagy inhibitor with an IC50 of 5.8 μM in the BxPC3 cells. It has antiproliferative activities in lung and pancreatic cancer cells.
Autophagy, 2021, 1-17
S8596 Autophinib Autophinib is a potent autophagy inhibitor with a novel chemotype with IC50 values of 90 and 40 nM for autophagy in starvation induced autophagy assay and rapamycin induced autophagy assay. The IC50 value for Vps34 is 19 nM in vitro.
Nat Genet, 2021, 53(4):435-444
J Agric Food Chem, 2021, 69(40):11847-11855
J Steroid Biochem Mol Biol, 2021, 209:105826
S8744 PHY34 PHY34 is a late-stage autophagy inhibitor with nanomolar potency and significant antitumor efficacy as a single agent against HGSOC in vivo.
S8764 IITZ-01 IITZ-01 is a potent autophagy inhibitor, enhancing autophagosome accumulation but inhibiting autophagosomal degradation by impairing lysosomal function.
Cancers (Basel), 2020, 12(9):E2363
S8793 ULK-101 ULK-101 is a potent and selective ULK1 inhibitor with IC50 values of 8.3 nM and 30 nM for ULK1 and ULK2, respectively.
J Virol, 2021, JVI0155021
Mol Carcinog, 2021, 10.1002/mc.23357
Cell Signal, 2021, 85:110040
S8807 PFK158 PFK158 is a potent and selective inhibitor of PFKFB3. It has improved PK properties and causes ~80% growth inhibition in several mouse models of human-derived tumors.
Front Immunol, 2021, 12:669456
Cancer Metab, 2021, 9(1):33
Cell Metab, 2020, 5;31(5):937-955e7
S8808 DC661 DC661 is capable of deacidifying the lysosome and inhibiting autophagy significantly better than hydroxychloroquine (HCQ). DC661 induces apoptosis.
Biomed Pharmacother, 2022, 145:112432
Nature, 2021, 10.1038/s41586-021-04204-9
Cell Death Dis, 2021, 12(3):239
S9150 Daurisoline Daurisoline, a bis-benzylisoquinoline alkaloid isolated from the rhizomes of Menispermum dauricum, is a potent autophagy blockers with antiarrhythmic effects.
S9424 Liensinine diperchlorate Liensinine, a major isoquinoline alkaloid, inhibits late-stage autophagy/mitophagy through blocking autophagosome-lysosome fusion. It is a novel autophagy/mitophagy inhibitor.
A5123 ATG9A Rabbit Recombinant mAb ATG9A Rabbit Recombinant mAb detects endogenous level of total ATG9A.
A5151 Atg4B Rabbit Recombinant mAb Atg4B Rabbit Recombinant mAb detects endogenous level of Atg4B.
S0012 E260 E260 (Fer and FerT inhibitor E260) is a Fer kinase and FerT inhibitor that selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level.
S0709 Tubastatin A TFA Tubastatin A TFA (Tubastatin A trifluoroacetate salt) is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
S1002 ABT-737 ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in cell-free assays, respectively; no inhibition observed against Mcl-1, Bcl-B or Bfl-1. ABT-737 induces mitochondrial pathway apoptosis and mitophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
Cell Death Dis, 2021, 12(8):736
Cell Death Dis, 2021, 12(11):1011
S1003 Linifanib (ABT-869) Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.
Cancer Lett, 2021, 507:80-88
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
S1004 Veliparib (ABT-888) Veliparib (ABT-888, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increases autophagy and apoptosis. Phase 3.
Cell, 2022, 185(1):169-183.e19
Transl Oncol, 2022, 15(1):101283
Sci Transl Med, 2021, 13(592)eabc7211
S1006 Saracatinib (AZD0530) Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM in cell-free assays, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). Saracatinib induces autophagy. Phase 2/3.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Nat Commun, 2021, 12(1):6941
S1009 Dactolisib (BEZ235) Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
Nat Commun, 2021, 12(1):7268
EMBO Mol Med, 2021, e14511
Cell Rep, 2021, 34(11):108870
S1011 Afatinib (BIBW2992) Afatinib (BIBW2992) inhibits EGFR/ErbB irreversibly in vitro with IC50 of 0.5, 0.4, 10, 14, 1 nM for EGFRwt, EGFR L858R , EGFR L858R/T790M ErbB2 (HER2) and ErbB4 (HER4), respectively. Afatinib induces autophagy.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(20)30609-7
Nat Cell Biol, 2021, 23(4):377-390
S1014 Bosutinib (SKI-606) Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.
Nat Commun, 2021, 12(1):6941
Cancer Res, 2021, 81(21):5438-5450
Cancer Res, 2021, canres.0613.2021
S1017 Cediranib (AZD2171) Cediranib (AZD2171, NSC-732208) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3 in HUVEC cells. Cediranib (AZD2171) induces autophagic vacuole accumulation. Phase 3.
Hum Mol Genet, 2021, ddab009
Sci Rep, 2021, 11(1):9362
Sci Rep, 2021, 11(1):23302
S1021 Dasatinib (BMS-354825) Dasatinib (BMS-354825) is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. Dasatinib induces autophagy and apoptosis with anti-tumor activity.
Nat Immunol, 2021, 10.1038/s41590-021-00948-8
Acta Neuropathol, 2021, 10.1007/s00401-021-02327-x
Nat Commun, 2021, 12(1):3705
S1023 Erlotinib HCl (OSI-744) Erlotinib HCl (OSI-744, CP358774, NSC 718781) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.
Nat Cell Biol, 2021, 23(4):377-390
Sci Adv, 2021, 7(10)eabe8671
Nat Commun, 2021, 12(1):4789
S1025 Gefitinib (ZD1839) Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.
Nature, 2021, 595(7869):730-734
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Cell Biol, 2021, 23(4):377-390
S1026 Imatinib (STI571) Mesylate Imatinib (STI571, CGP057148B, Gleevec) Mesylate is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. Imatinib Mesylate (STI571) induces autophagy.
Cancer Cell, 2021, S1535-6108(21)00659-0
Clin Cancer Res, 2021, 27(9):2533-2548
Cell Rep, 2021, 37(1):109788
S1027 FL-411 FL-411 (BRD4-IN-1) is a potent and selective inhibitor of Bromodomain-containing protein 4 (BRD4) with IC50 of 0.43 μM for BRD4(1). FL-411 induces ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction.
S1030 Panobinostat (LBH589) Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.
Nat Med, 2021, 10.1038/s41591-020-01212-6
Cell Stem Cell, 2021, 28(1):48-62.e6
Hepatology, 2021, 10.1002/hep.32245
S1033 Nilotinib (AMN-107) Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
Cancer Cell, 2021, S1535-6108(21)00659-0
EMBO Mol Med, 2021, e11814
Cancer Res, 2021, canres.1222.2021
S1035 Pazopanib HCl (GW786034 HCl) Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces autophagic Type II cell death.
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancers (Basel), 2021, 13(14)3635
J Clin Endocrinol Metab, 2021, dgab020
S1038 PI-103 PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. PI-103 induces apoptosis in murine T-cell Lymphoma.
Adv Healthc Mater, 2021, e2101944
Cell Chem Biol, 2021, S2451-9456(21)00254-3
Neurobiol Dis, 2021, 156:105407
S1039 Rapamycin (AY-22989) Rapamycin (AY-22989, Rapamune, Sirolimus, NSC-2260804) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
J Cell Biol, 2022, 221(1)e202103033
Bone, 2022, 154:116262
Neural Regen Res, 2022, 17(4):824-831
S1040 Sorafenib (BAY 43-9006) tosylate Sorafenib (BAY 43-9006) tosylate is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
Cancer Cell, 2021, S1535-6108(21)00659-0
Leukemia, 2021, 10.1038/s41375-021-01308-z
Theranostics, 2021, 11(12):5650-5674
S1044 Temsirolimus (CCI-779) Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis.
Mol Syst Biol, 2021, 17(8):e10239
Cell Death Dis, 2021, 12(1):108
J Clin Endocrinol Metab, 2021, dgab020
S1046 Vandetanib (ZD6474) Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).
J Clin Endocrinol Metab, 2021, dgab020
Cell Chem Biol, 2021, S2451-9456(21)00303-2
Cancer Discov, 2021, candisc.1201.2020
S1047 Vorinostat (SAHA) Vorinostat (suberoylanilide hydroxamic acid, SAHA, MK0683, Zolinza) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
Adv Sci (Weinh), 2021, e2103360
Hepatology, 2021, 10.1002/hep.32245
Nat Commun, 2021, 12(1):4404
S1048 Tozasertib (VX-680, MK-0457) Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
J Cell Biol, 2021, 220(2)e202008029
EMBO Rep, 2021, e51503
S1049 Y-27632 2HCl Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM in a cell-free assay, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK.
Nature, 2021, 600(7888):285-289
Nature, 2021, 593(7859):440-444
Cell, 2021, 184(25):6119-6137.e26
S1053 Entinostat (MS-275) Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Science, 2021, 372(6537)eaba1786
Nat Chem Biol, 2021, 10.1038/s41589-021-00772-z
Nat Commun, 2021, 12(1):2699
S1057 Obatoclax Mesylate (GX15-070) Obatoclax Mesylate (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 3.
Cancer Res, 2021, canres.0955.2021
Transl Oncol, 2021, 14(8):101116
Biomaterials, 2020, 232:119709
S1060 Olaparib (AZD2281) Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutations.
Cell, 2022, 185(1):169-183.e19
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
S1065 Pictilisib (GDC-0941) Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Immunity, 2021, 54(8):1807-1824.e14
S1068 Crizotinib (PF-02341066) Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Nature, 2021, 600(7888):319-323
Cell, 2021, 184(10):2649-2664.e18
Nat Commun, 2021, 12(1):6813
S1069 Luminespib (NVP-AUY922) Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.
Cell Rep, 2021, 34(11):108870
Haematologica, 2021, 10.3324/haematol.2021.278743
Cancers (Basel), 2021, 13(15)3850
S1075 SB216763 SB216763 is a potent and selective GSK-3 inhibitor with IC50 of 34.3 nM for GSK-3α and equally effective at inhibiting human GSK-3β. SB216763 activates autophagy.
Biomed Pharmacother, 2022, 145:112432
J Clin Invest, 2021, 131(6)136098
Autophagy, 2021, 1-19
S1077 SB202190 (FHPI) SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM in cell-free assays, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo. SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. SB202190 significantly suppresses Erastin‐dependent ferroptosis.
Nature, 2021, 600(7888):314-318
Immunity, 2021, S1074-7613(21)00210-7
Nat Commun, 2021, 12(1):6941
S1078 MK-2206 2HCl MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. MK-2206 2HCl induces autophagy and apoptosis in cancer cells. Phase 2.
Cancer Cell, 2021, S1535-6108(21)00383-4
Immunity, 2021, S1074-7613(21)00069-8
Cell Res, 2021, 10.1038/s41422-021-00528-3
S1080 SU11274 SU11274 (PKI-SU11274) is a selective Met (c-Met) inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. SU11274 induces autophagy, apoptosis and cell cycle arrest.
Cell Rep, 2021, 37(5):109905
Signal Transduct Target Ther, 2021, 6(1):401
Cell Chem Biol, 2021, S2451-9456(21)00303-2
S1085 Belinostat (PXD101) Belinostat (PXD101, NSC726630, PX-105684) is a novel HDAC inhibitor with IC50 of 27 nM in a cell-free assay, with activity demonstrated in cisplatin-resistant tumors. Belinostat (PXD101) induces autophagy.
Adv Sci (Weinh), 2021, e2103360
Hepatology, 2021, 10.1002/hep.32245
Nat Commun, 2021, 12(1):117
S1107 Danusertib (PHA-739358) Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2.
Cancers (Basel), 2021, 13(6)1205
Life Sci Alliance, 2021, 4(8)e202101019
Mol Cell, 2020, 80(6):1104-1122.e9
S1120 Everolimus (RAD001) Everolimus (RAD001, SDZ-RAD) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay. Everolimus induces cell apoptosis and autophagy and inhibits tumor cells proliferation.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Gut, 2021, gutjnl-2020-322660
S1122 Mocetinostat (MGCD0103) Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.
Cancer Cell, 2021, S1535-6108(20)30662-0
Nat Commun, 2021, 12(1):5056
Cancers (Basel), 2021, 13(15)3862
S1129 SRT1720 HCl SRT1720 HCl is a selective SIRT1 activator with EC50 of 0.16 μM in a cell-free assay, but is >230-fold less potent for SIRT2 and SIRT3. SRT1720 induces autophagy.
Neuro Oncol, 2021, 23(1):53-62
Theranostics, 2021, 11(2):893-905
Oncogene, 2021, 10.1038/s41388-021-01999-9
S1130 YM155 (Sepantronium Bromide) YM155 (Sepantronium Bromide) is a potent survivin suppressant by inhibiting Survivin promoter activity with IC50 of 0.54 nM in HeLa-SURP-luc and CHO-SV40-luc cells; does not significantly inhibit SV40 promoter activity, but is observed to slightly inhibit the interaction of Survivin with XIAP. YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells. Phase 2.
Nat Commun, 2021, 12(1):2877
Nat Commun, 2021, 12(1):2475
J Clin Invest, 2021, 131(10)146777
S1133 Alisertib (MLN8237) Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Cancer Cell, 2021, S1535-6108(21)00338-X
S1135 Pemetrexed (LY-231514) disodium Pemetrexed (LY-231514) disodium is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.
J Exp Clin Cancer Res, 2021, 40(1):344
Br J Cancer, 2021, 10.1038/s41416-021-01441-7
Cell Chem Biol, 2021, S2451-9456(21)00442-6
S1141 Tanespimycin (17-AAG) Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.
Cell Stem Cell, 2021, S1934-5909(21)00294-0
Mol Cell, 2021, 81(6):1170-1186.e10
EMBO Rep, 2021, e51740
S1149 Gemcitabine (LY-188011) HCl Gemcitabine (LY-188011, NSC 613327) HCl is a DNA synthesis inhibitor with IC50 of 50 nM, 40 nM, 18 nM and 12 nM in PANC1, MIAPaCa2, BxPC3 and Capan2 cells, respectively.
Cell, 2021, 184(25):6119-6137.e26
Nat Commun, 2021, 12(1):4917
Nat Commun, 2021, 12(1):1602
S1166 Cisplatin (NSC 119875) Cisplatin (NSC 119875, Cisplatinum, cis-diamminedichloroplatinum II, CDDP, cis DDP, DDP) is an inorganic platinum complex, which is able to inhibit DNA synthesis by conforming DNA adducts in tumor cells. Cisplatin activates ferroptosis and induces autophagy. Solutions are best fresh-prepared.
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Commun, 2021, 12(1):5404
Nat Commun, 2021, 12(1):7064
S1168 Valproic Acid (NSC 93819) sodium salt Valproic Acid sodium salt (NSC 93819, Sodium valproate) is a HDAC inhibitor by selectively inducing proteasomal degradation of HDAC2, used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. Valproic acid induces Notch1 signaling in small cell lung cancer (SCLC) cells. Valproic acid is under investigation for treatment of HIV and various cancers. Valproic acid (VPA) induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α.
Pigment Cell Melanoma Res, 2021, 10.1111/pcmr.13014
Front Immunol, 2021, 12:771453
Front Oncol, 2021, 11:723966
S1178 Regorafenib (BAY 73-4506) Regorafenib (BAY 73-4506, Fluoro-Sorafenib, Resihance, Stivarga) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy.
Cancer Cell, 2021, S1535-6108(21)00659-0
Adv Sci (Weinh), 2021, e2103360
ACS Appl Mater Interfaces, 2021, 13(41):48478-48491
S1190 Bicalutamide (ICI-176334) Bicalutamide (ICI-176334) is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. Bicalutamide promotes autophagy.
Sci Adv, 2021, 7(27)eabg2564
Cell Rep, 2021, 36(10):109625
Cancer Lett, 2021, 520:172-183
S1191 Fulvestrant (ICI-182780) Fulvestrant (ICI-182780, ZD 9238, ZM 182780) is an estrogen receptor (ER) antagonist with IC50 of 0.94 nM in a cell-free assay. Fulvestrant also induces autophagy and apoptosis and has antitumor activity.
Biochim Biophys Acta Gen Subj, 2022, 1866(1):130046
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-2961
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
S1218 Clofarabine Clofarabine (Clolar) inhibits the enzymatic activities of ribonucleotide reductase (RNR) (IC50 = 65 nM) and DNA polymerase. Clofarabine induces autophagy and apoptosis.
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
iScience, 2021, 24(9):103080
S1219 YM201636 YM201636 is a selective PIKfyve inhibitor with IC50 of 33 nM, less potent to p110α and insensitive to Fabl (yeast orthologue). YM-201636 suppresses the growth of liver cancer via the induction of autophagy.
Cell Rep, 2021, 35(1):108940
Front Oncol, 2021, 11:620873
J Biol Methods, 2021, 8(1):e143
S1224 Oxaliplatin (NSC 266046) Oxaliplatin (NSC 266046, L-OHP, Eloxatin) is a DNA alkylating agent that activates autophagy. Oxaliplatin inhibits DNA synthesis by conforming DNA adducts in RT4, TCCSUP, A2780, HT-29, U-373MG, U-87MG, SK-MEL-2, and HT-144 cells. DMF is recommended for dissolution. Solutions are best fresh-prepared.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Adv Sci (Weinh), 2021, e2103360
S1225 Etoposide (VP-16) Etoposide (VP-16, VP-16213) is a semisynthetic derivative of podophyllotoxin, which inhibits DNA synthesis via topoisomerase II inhibition activity. Etoposide induces autophagy, mitophagy and apoptosis.
Nature, 2021, 10.1038/s41586-021-04204-9
Nature, 2021, 10.1038/s41586-021-04009-w
Cancer Cell, 2021, S1535-6108(21)00659-0
S1228 Idarubicin HCl Idarubicin HCl (4-demethoxydaunorubicin, NSC256439, 4-DMDR) is a hydrochloride salt form of Idarubicin which is an anthracycline antibiotic and a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells with IC50 of 3.3 ng/mL in a cell-free assay. Idarubicin induces mTOR-dependent cytotoxic autophagy.
Cancers (Basel), 2021, 13(14)3586
Biomolecules, 2021, 11(8)1128
Int J Mol Sci, 2021, 22(3)1362
S1230 Flavopiridol (L86-8275) Flavopiridol (L86-8275, Alvocidib, NSC 649890, HMR-1275) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol induces autophagy and ER stress. Flavopiridol blocks HIV-1 replication. Phase 1/2.
Nature, 2021, 10.1038/s41586-021-03445-y
Genome Res, 2021, 31(6):981-994
J Cell Biol, 2021, 220(7)e202008146
S1231 Topotecan (NSC609699) HCl Topotecan HCl (NSC609699, Nogitecan, SKFS 104864A) is a topoisomerase I inhibitor for MCF-7 Luc cells and DU-145 Luc cells with IC50 of 13 nM and 2 nM in cell-free assays, respectively. Topotecan HCl induces autophagy and apoptosis.
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancer Res, 2021, canres.1540.2020
Cell Rep, 2021, 34(10):108814
S1233 2-Methoxyestradiol (2-MeOE2) 2-Methoxyestradiol (2-MeOE2, NSC 659853, 2-ME2) depolymerizes microtubules and blocks HIF-1α nuclear accumulation and HIF-transcriptional activity. 2-Methoxyestradiol induces both autophagy and apoptosis in various carcinogenic cell lines. Phase 2.
Cell Death Differ, 2021, 10.1038/s41418-021-00885-x
Cancers (Basel), 2021, 13(20)5232
Cell Death Discov, 2021, 7(1):242
S1235 Letrozole (CGS 20267) Letrozole (CGS 20267) is a third generation inhibitor of aromatase with IC50 of 0.07-20 nM in cell-free assays.It has no effect on the plasma levels of 17α-OH progesterone, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), or androstenedione and does not affect normal urine electrolyte excretion or thyroid function in clinical studies. Letrozole induces autophagy.
Mol Hum Reprod, 2021, 27(4)gaab013
Steroids, 2021, 177:108935
Hum Cell, 2021, 10.1007/s13577-021-00639-4
S1237 Temozolomide (CCRG 81045) Temozolomide (CCRG81045, NSC 362856, TMZ) is a monofunctional SN-1 alkylating agent that can modify nitrogen atoms in the DNA ring and the extracyclic oxygen group, chemically converted to MTIC and degrades to methyldiazonium cation, which transfers methyl groups to DNA at physiologic pH. A DNA damage inducer in L-1210 and L-1210/BCNU cells. Temozolomide induces apoptosis and exhibits antitumor activity.
Cell Res, 2021, 10.1038/s41422-021-00528-3
Clin Cancer Res, 2021, clincanres.2092.2021
Theranostics, 2021, 11(4):1991-2005
S1238 Tamoxifen (ICI 46474) Tamoxifen (ICI 46474, (Z)-Tamoxifen, trans-Tamoxifen) is a selective estrogen receptor modulator (SERM). Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis.
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
Cancers (Basel), 2021, 13(9)2116
Cell Death Dis, 2021, 12(6):619
S1250 Enzalutamide (MDV3100) Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is shown to increase autophagy.
Nat Med, 2021, 27(3):426-433
Nat Med, 2021, 10.1038/s41591-020-01168-7
J Extracell Vesicles, 2021, 10(10):e12136
S1263 CHIR-99021 (CT99021) CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. CHIR99021 functions as a Wnt/β-catenin activator and induces autophagy.
Cell, 2021, 184(11):2843-2859.e20
Nat Genet, 2021, 53(12):1686-1697
Nat Genet, 2021, 53(4):467-476
S1267 Vemurafenib (PLX4032) Vemurafenib (PLX4032, RG7204, RO5185426) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00837-3
Cancer Cell, 2021, S1535-6108(21)00659-0
Cell Metab, 2021, S1550-4131(21)00180-7
S1290 Celastrol (NSC 70931) Celastrol (NSC 70931, Tripterine) is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy.
Mol Oncol, 2021, 10.1002/1878-0261.12936
Aging (Albany NY), 2021, 13(12):16816-16833
Molecules, 2021, 26(14)4124
S1312 Streptozotocin (STZ) Streptozotocin (STZ, NSC-85998, Streptozocin, U 9889) is a glucosamine-nitrosourea derivative, which is a DNA-methylating, carcinogenic, antibiotic and diabetes inducing agent. Streptozotocin induces autophagy and apoptosis. Solutions are best fresh-prepared.
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Epigenomics, 2020, 12(20):1811-1824
S1314 Zoledronic acid (ZOL 446) Zoledronic acid (ZOL 446, ZA, Zoledronate, CGP-4244, GP42446A, Zometa, Zomera, Aclasta, Reclast), a potent osteoclast inhibitor, induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho. Zoledronic acid (ZA) also induces autophagy.
Biomater Sci, 2021, 10.1039/d0bm02107e
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
S1322 Dexamethasone (MK-125) Dexamethasone (MK-125, NSC 34521, Hexadecadrol, Prednisolone F) is a potent synthetic member of the glucocorticoid class of steroid drugs, and an interleukin receptor modulator that has anti-inflammatory and immunosuppressant effects. Dexamethasone induces autophagy and mitophagy. Dexamethasone is tested in hospitalized patients with COVID-19 and is found to have benefits for critically ill patients.
Mol Syst Biol, 2021, 17(9):e10426
Cell Rep, 2021, 36(2):109360
Cell Rep, 2021, 37(5):109912
S1351 Ivermectin (MK-933) Ivermectin (MK-933, IVM) is a glutamate-gated chloride channel (GluCls) activator, used as a broad-spectrum antiparasitic drug. Ivermectin (MK-933, IVM) is a specific positive allosteric effector of P2X4 and α7 nicotinic acetylcholine receptors (nAChRs). Ivermectin has potent antiviral activity towards both HIV-1 and dengue virus. Ivermectin induces autophagy through the AKT/mTOR signaling pathway and mitophagy.
J Virol, 2021, JVI0148121
BMC Cancer, 2021, 21(1):1307
Nat Cell Biol, 2020,
S1378 Ruxolitinib (INCB018424) Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Cancer Cell, 2021, S1535-6108(21)00492-X
Sci Immunol, 2021, 6(59)eabi9007
Sci Adv, 2021, 7(50):eabl5182
S1389 Omeprazole Omeprazole is a proton pump inhibitor that blocks H(+)-K(+)-ATPase, used to treat dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, laryngopharyngeal reflux, and Zollinger–Ellison syndrome.
Theranostics, 2021, 11(5):2364-2380
J Virol, 2021, JVI.00190-21
Biosci Rep, 2021, BSR20200842
S1396 Resveratrol (SRT501) Resveratrol (SRT501, trans-Resveratrol) has a wide spectrum of targets including cyclooxygenases(i.e. COX, IC50=1.1 μM), lipooxygenases(LOX, IC50=2.7 μM), kinases, sirtuins and other proteins. It has anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects. Resveratrol induces mitophagy/autophagy and autophagy-dependent apoptosis.
Adv Sci (Weinh), 2021, e2103360
Front Immunol, 2021, 12:685523
Int J Mol Sci, 2021, 22(5)2354
S1403 Tigecycline (GAR-936) Tigecycline (GAR-936) is bacteriostatic and is a protein synthesis inhibitor by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation. Tigecycline induces autophagy by downregulating the PI3K-AKT-mTOR pathway.
iScience, 2021, 24(11):103350
Biomolecules, 2020, 10(10)E1395
Aging (Albany NY), 2020, 12(12):11364-11385
S1555 AZD8055 AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.
Nature, 2021, 591(7849):288-292
Immunity, 2021, S1074-7613(21)00069-8
Sci Adv, 2021, 7(40):eabj2485
S1573 Fasudil (HA-1077) HCl Fasudil (HA-1077, AT-877), a potent and selective inhibitor of Rho kinase, displays less potent inhibiton over PKA, PKG, PKC and MLCK with Ki of 1.6, 1.6, 3.3, and 36 μM in cell-free assays, respectively. Fasudil is also a calcium channel blocker.
Proc Natl Acad Sci U S A, 2021, 118(2)e2016034118
J Neurochem, 2021, 10.1111/jnc.15436
Front Microbiol, 2021, 12:775083
S1576 Sulfasalazine (NSC 667219) Sulfasalazine (NSC 667219, Azulfidine, Salazopyrin, Sulphasalazine) is a sulfa derivative of mesalazine, used as an anti-inflammatory agent to treat bowel disease and rheumatoid arthritis. Sulfasalazine is a potent and specific inhibitor of nuclear factor kappa B (NF-κB), TGF-β and COX-2. Sulfasalazine induces ferroptosis, apoptosis and autophagy.
Cell Metab, 2021, S1550-4131(21)00233-3
Sci Adv, 2021, 7(35)eabj0364
Sci Adv, 2021, 7(27)eabh3032
S1582 H 89 2HCl H 89 2HCl is a potent PKA inhibitor with Ki of 48 nM in a cell-free assay, 10-fold selective for PKA than PKG,500-fold greater selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II. H 89 2HCl induces autophagy.
Sci Immunol, 2021, 6(61)eabg9698
Theranostics, 2021, 11(10):4975-4991
Cell Rep, 2021, 37(12):110137
S1590 TWS119 TWS119 is a GSK-3β inhibitor with IC50 of 30 nM in a cell-free assay; capable of inducing neuronal differentiation and may be useful to stem cell biology. GSK-3β inhibition triggers autophagy.
Nat Commun, 2021, 12(1):4536
EMBO Rep, 2021, e51503
Cell Rep, 2021, 36(1):109311
S1648 Cytarabine (U-19920A) Cytarabine (U-19920A, Cytarabin, Ara-C, Arabinofuranosyl Cytidine, Cytosine β-D-arabinofuranoside, Cytosine arabinoside, NSC 63878, NSC 287459) is an antimetabolic agent and DNA synthesis inhibitor with IC50 of 16 nM in wild-type CCRF-CEM cells. Cytarabine induces autophagy and apoptosis.
Leukemia, 2021, 10.1038/s41375-021-01361-8
Blood Cancer J, 2021, 11(6):111
Cell Rep, 2021, 36(7):109559
S1693 Carbamazepine Carbamazepine (Carbatrol, NSC 169864) is a sodium channel blocker with IC50 of 131 μM in rat brain synaptosomes.
Front Pharmacol, 2021, 12:749930
Anticancer Res, 2021, 41(2):687-697
PLoS One, 2019, 14(2):e0211644
S1714 Gemcitabine (LY-188011) Gemcitabine (LY-188011, NSC 613327), a nucleic acid synthesis inhibitor, is a very potent and specific deoxycytidine analogue, used as chemotherapy. Gemcitabine induces a potent p53-dependent apoptosis.
Nat Commun, 2021, 12(1):1602
Cancer Res, 2021, canres.1337.2021
Cell Rep, 2021, 34(10):108814
S1747 Nimodipine Nimodipine (BAY E 9736) is a dihydropyridine calcium channel blocker and an autophagy inhibitor, used in the treatment of high blood pressure.
Cell Discov, 2020, 6(1):96
G3 (Bethesda), 2020, 4;10(5):1585-1597
Antiviral Res, 2016, 132:38-45
S1759 Pitavastatin (NK-104) calcium Pitavastatin Calcium (NK-104, P-872441, itavastatin, nisvastatin), a novel member of the medication class of statins, is a calcium salt formulation of pitavastatin which is a highly effective HMG-CoA reductase inhibitor. Pitavastatin Calcium attenuates AGEs-induced mitophagy via inhibition of ROS generation. Pitavastatin Calcium induces autophagy and apoptosis.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Cancer Discov, 2021, candisc.0551.2021
Transl Oncol, 2021, 14(7):101107
S1782 Azacitidine (5-Azacytidine) Azacitidine (5-Azacytidine, 5-AzaC, Ladakamycin, AZA, 5-Aza, CC-486) is a nucleoside analogue of cytidine that specifically inhibits DNA methylation by trapping DNA methyltransferases. Azacitidine induces mitochondrial apoptosis and autophagy.
Clin Cancer Res, 2021, clincanres.2486.2019
Int J Cancer, 2021, 10.1002/ijc.33865
J Hematol Oncol, 2021, 14(1):70
S1792 Simvastatin (MK 733) Simvastatin (MK-0733, MK 733) is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Theranostics, 2021, 11(4):1609-1625
Theranostics, 2021, 11(13):6560-6572
S1794 Fenofibrate (NSC-281319) Fenofibrate (NSC-281319) is a compound of the fibrate class and fibric acid derivative. Fenofibrate is a selective agonist of PPARα with EC50 of 30 μM. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with IC50 of 0.2 μM, 0.7 μM and 9.7 μM for CYP2C19, CYP2B6 and CYP2C9, respectively. Fenofibrate induces autophagy.
Redox Biol, 2021, 46:102082
J Cell Mol Med, 2020, 24(6):3384-3398
J Cell Mol Med, 2020, 24(6):3384-3398
S1837 Flubendazole Flubendazole (Flumoxanal, NSC 313680) is an autophagy inducer by targeting Atg4B, used to treat internal parasite and worm infection.
Sci Rep, 2020, 10(1):13124
RSC Advances, 2018, 10.1039/C7RA12259D
S1847 Clemastine (HS-592) fumarate Clemastine Fumarate (HS-592, Meclastine) is a selective histamine H1 receptor antagonist with IC50 of 3 nM. Clemastine stimulates autophagy via mTOR pathway.
Neuron, 2021, S0896-6273(21)00352-4
Neurosci Bull, 2021, 10.1007/s12264-021-00745-1
Neurochem Res, 2021, 10.1007/s11064-021-03465-0
S1848 Curcumin Curcumin (Diferuloylmethane, Natural Yellow 3, Turmeric yellow) is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family (Zingiberaceae). It is an inhibitor of p300 histone acetylatransferase(IC50~25 μM)and Histone deacetylase (HDAC); activates Nrf2 pathway and supresses the activation of NF-κB. Curcumin induces mitophagy, autophagy, apoptosis, and cell cycle arrest with antitumor activity. Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis-mediated cell death. Curcumin exhibits anti-infective properties against various human pathogens like the influenza virus, hepatitis C virus, HIV and so on.
Adv Sci (Weinh), 2021, e2103360
Front Immunol, 2021, 12:656242
Aging (Albany NY), 2021, 13(10):13968-14000
S1896 Hydroxyurea (NSC-32065) Hydroxyurea (NSC-32065, NCI-C04831, Hydroxycarbamide) is an antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxyurea activates apoptosis and autophagy. Hydroxyurea is used to treat HIV infection.
Nat Commun, 2021, 12(1):5572
Cancer Res, 2021, canres.3761.2020
Cell Death Dis, 2021, 12(2):183
S1950 Metformin HCl Metformin HCl (1,1-Dimethylbiguanide HCl) decreases hyperglycemia in hepatocytes primarily by suppressing glucose production by the liver (hepatic gluconeogenesis). Metformin promotes mitophagy in mononuclear cells. Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153.
Immunity, 2021, S1074-7613(21)00210-7
Cell Res, 2021, 10.1038/s41422-021-00565-y
Mol Cell, 2021, S1097-2765(21)00232-X
S1972 Tamoxifen (ICI 46474) Citrate Tamoxifen Citrate (ICI 46474) is a selective estrogen receptor modulator (SERM). Tamoxifen Citrate is also a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis and autophagy.
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
Cancers (Basel), 2021, 13(9)2116
Cell Death Dis, 2021, 12(6):619
S1979 Amiodarone (NSC 85442) HCl Amiodarone (NSC 85442) HCl is a sodium/potassium-ATPase inhibitor and an autophagy activator, used to treat various types of cardiac dysrhythmias.
Front Cell Infect Microbiol, 2021, 11:630812
Drug Metab Dispos, 2020, 48(8):613-621
Cell Syst, 2019, 8(2):97-108
S1999 Sodium butyrate Sodium butyrate (NaB, Butanoic acid sodium salt), sodium salt of butyric acid, is a histone deacetylase inhibitor and competitively binds to the zinc sites of class I and II histone deacetylases (HDACs). Sodium butyrate (NaB) inhibits cell cycle progression, promotes differentiation, and induces apoptosis and autophagy in several types of cancer cells.
Cell Mol Life Sci, 2021, 10.1007/s00018-021-03883-x
Front Cell Dev Biol, 2021, 9:662868
Int J Mol Sci, 2020, 21(2)
S2061 Lovastatin (MK-803) Lovastatin (MK-803, Mevinolin) is an inhibitor of HMG-CoA reductase with IC50 of 3.4 nM in a cell-free assay, used for lowering cholesterol (hypolipidemic agent). Lovastatin triggers autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Sci Adv, 2021, 7(29)eabg3188
Cancer Res, 2021, canres.0955.2021
S2077 Atorvastatin Calcium Atorvastatin Calcium is an inhibitor of HMG-CoA reductase used as a cholesterol-lowering medication that blocks the production of cholesterol. Atorvastatin Calcium induces apoptosis and autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Oncol Lett, 2021, 21(2):82
Neurobiol Dis, 2021, 152:105294
S2111 Lapatinib (GW-572016) Lapatinib (GW-572016, GSK572016, GW2016), used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death.
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Cell Biol, 2021, 23(4):377-390
Gut, 2021, 70(5):890-899
S2163 PF-4708671 PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. PF-4708671 induces autophagy. First S6K1-specific inhibitor to be reported.
Mol Cell, 2021, S1097-2765(21)00497-4
Cancers (Basel), 2021, 13(8)1909
Cell Death Dis, 2021, 12(1):108
S2180 Ixazomib (MLN2238) Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Ixazomib (MLN2238) induces autophagy. Phase 3.
Pharmaceutics, 2021, 13(3)314
Biomedicines, 2021, 9(1)E33
Cell, 2020, 182(3):685-712.e19
S2181 Ixazomib Citrate (MLN9708) Analogue Ixazomib Citrate (MLN9708) Analogue is the analogue of Ixazomib Citrate (MLN9708) from WO2016165677A1. Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/Ki of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.
Autophagy, 2021, 1-19
Cell Chem Biol, 2021, S2451-9456(21)00400-1
S2198 SGI-1776 free base SGI-1776 free base is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM in a cell-free assay, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin. SGI-1776 induces apoptosis and autophagy. Phase 1.
Cancer Res, 2021, canres.1023.2021
Commun Biol, 2021, 4(1):1221
Cell, 2020, 182(3):685-712.e19
S2218 Torkinib (PP242) Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and apoptosis.
Immunity, 2021, 54(10):2354-2371.e8
Sci Adv, 2021, 7(46):eabi6439
Mol Cancer, 2021, 20(1):85
S2219 Momelotinib (CYT387) Momelotinib (CYT387, LM-1149 , CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.
Cell Stem Cell, 2021, S1934-5909(21)00344-1
Cancer Res, 2021, canres.0955.2021
J Transl Med, 2021, 19(1):396
S2226 Idelalisib (CAL-101, GS-1101) Idelalisib (CAL-101, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Mol Cell, 2021, 81(4):708-723.e5
J Exp Med, 2021, 218(12)e20211035
J Exp Med, 2021, 218(2)e20200517
S2248 Silmitasertib (CX-4945) Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, less potent to Flt3, Pim1 and CDK1 (inactive in cell-based assay). Silmitasertib induces autophagy and promotes apoptosis. Phase 1/2.
Genes Dev, 2021, 35(15-16):1123-1141
Elife, 2021, 10e65962
J Med Chem, 2021, 10.1021/acs.jmedchem.1c00063
S2285 Cryptotanshinone Cryptotanshinone is a STAT3 inhibitor with IC50 of 4.6 μM in a cell-free assay, strongly inhibits phosphorylation of STAT3 Tyr705, with a small effect on STAT3 Ser727, but none against STAT1 nor STAT5. Cryptotanshinone induces ROS-dependent autophagy and mitochondria-mediated apoptosis.
Front Immunol, 2021, 12:712781
Int J Biol Sci, 2021, 17(10):2417-2429
J Cell Mol Med, 2021, 10.1111/jcmm.16250
S2290 Dihydroartemisinin (DHA) Dihydroartemisinin (DHA, Dihydroqinghaosu, β-Dihydroartemisinin, Artenimol) is a semi-synthetic derivative of artemisinin and isolated from the traditional Chinese herb Artemisia annua. Dihydroartemisinin induces autophagy and apoptosis by suppressing NF-κB activation.
Nat Immunol, 2021, 10.1038/s41590-021-00967-5
ACS Infect Dis, 2021, 10.1021/acsinfecdis.0c00580
Mol Med Rep, 2021, 23(1)40
S2310 Honokiol (NSC 293100) Honokiol (NSC 293100) is the active principle of magnolia extract that inhibits Akt-phosphorylation and promotes ERK1/2 phosphorylation. Honokiol causes G0/G1 phase arrest, induces apoptosis, and autophagy via the ROS/ERK1/2 signaling pathway. Honokiol inhibits hepatitis C virus (HCV) infection. Phase 3.
Cell Death Dis, 2021, 12(9):847
Front Cell Dev Biol, 2021, 9:619475
Am J Cancer Res, 2021, 11(6):3039-3054
S2391 Quercetin (NSC 9221) Quercetin (NSC 9221, Sophoretin, C.I. 75720), a natural flavonoid present in vegetables, fruit and wine, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4-5.4 μM. Quercetin induces mitophagy, apoptosis and protective autophagy. Phase 4.
Nucleic Acids Res, 2021, gkab538
Redox Biol, 2021, 44:102010
Front Immunol, 2021, 12:685523
S2449 Colforsin (Forskolin, HL 362) Colforsin (Forskolin, HL 362, Coleonol, Colforsin) is a ubiquitous activator of eukaryotic adenylyl cyclase (AC) in a wide variety of cell types, commonly used to raise levels of cAMP in the study and research of cell physiology. Forskolin also activates PXR and FXR activity. Forskolin stimulates autophagy.
Adv Sci (Weinh), 2021, e2100190
Sci Adv, 2021, 7(33)eabf4416
Eur Respir J, 2021, 2100908
S2458 Clonidine HCl Clonidine HCl is a direct-acting α2 adrenergic agonist with an ED50 of 0.02±0.01 mg/kg.
S2475 Imatinib (STI571) Imatinib (STI571, CGP057148B, Gleevec) is a multi-target inhibitor of tyrosine kinase with inhibition for v-Abl, c-Kit and PDGFR, IC50 values are 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. Imatinib (STI571) induces autophagy.
Cell Host Microbe, 2021, 29(6):941-958.e10
Nat Commun, 2021, 12(1):51
Clin Cancer Res, 2021, 27(9):2533-2548
S2476 Itraconazole (R 51211) Itraconazole (R 51211) is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. Itraconazole is a potent antagonist of the Hedgehog (Hh) signaling pathway. Itraconazole suppresses the growth of glioblastoma through induction of autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Sci Rep, 2021, 11(1):17665
Front Microbiol, 2021, 12:649026
S2480 Loperamide HCl Loperamide HCl (ADL 2-1294) is a selective μ-opioid receptor agonist opioid with Ki of 3.3 nM, 15-fold and 350-fold selective over the δ subtype and the κ subtype of the opioid receptor, used against diarrhea resulting from gastroenteritis or inflammatory bowel disease.
bioRxiv, 2020, 2020/9/20.4.7.30734
Exp Ther Med, 2019, 17(2):1312-1320
Nutrients, 2017, 9(12)
S2491 Nitrendipine Nitrendipine (Bayotensin) is a dihydropyridine calcium channel blocker with an IC50 of 95 nM.
S2505 Rosiglitazone (BRL-49653) maleate Rosiglitazone maleate (BRL 49653), a member of the thiazolidinedione class of antihyperglycaemic agents, is a high-affinity selective agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ) with IC50 of 42 nM. Rosiglitazone maleate also modulates TRP channels and induces autophagy. Rosiglitazone prevents ferroptosis.
Cell Death Dis, 2021, 12(11):972
Antioxidants (Basel), 2021, 10(2)155
Front Cardiovasc Med, 2021, 8:698056
S2556 Rosiglitazone (BRL 49653) Rosiglitazone (BRL 49653) is a potent antihyperglycemic agent and a potent thiazolidinedione insulin sensitizer with IC50 of 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha-binding action. Rosiglitazone modulates TRP channels and induces autophagy. Rosiglitazone prevents ferroptosis.
Toxicology, 2022, 465:153048
Sci Adv, 2021, 7(35)eabj0364
Cell Death Dis, 2021, 12(11):972
S2606 Mifepristone (RU486) Mifepristone (RU486, C-1073, RU 38486, Mifegyne) is a remarkably active antagonist of progesterone receptor and glucocorticoid receptor with IC50 of 0.2 nM and 2.6 nM, respectively. Mifepristone promotes cell autophagy and apoptosis, decreases Bcl-2 level and increases Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1.
Nat Commun, 2021, 12(1):7041
Exp Eye Res, 2021, S0014-4835(21)00331-6
Oncol Rep, 2021, 46(3)202
S2619 MG-132 MG132 (Z-Leu-Leu-Leu-al) is a potent cell-permeable proteasome and calpain inhibitor with IC50s of 0.1 μM and 1.2 μM for the inhibition of proteasome and calpain, respectively. MG132 activates autophagy and induces apoptosis in tumor cells.
Theranostics, 2022, 12(2):976-998
FASEB J, 2022, 36(1):e22087
Biomed Pharmacother, 2022, 145:112432
S2624 OSI-027 OSI-027 (ASP4786, CERC 006, AEVI-006) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM in cell-free assays, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. OSI-027 induces autophagy in cancer cells. Phase 1.
Cell Death Discov, 2021, 7(1):201
Mol Ther Nucleic Acids, 2020, 1;20:801-811
Proc Natl Acad Sci U S A, 2019, 10.1073/pnas.1911393116
S2626 Rabusertib (LY2603618) Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.
Nat Genet, 2021, 10.1038/s41588-021-00893-0
Cancer Cell, 2021, S1535-6108(21)00383-4
Nucleic Acids Res, 2021, gkab643
S2635 CCT128930 CCT128930 is a potent, ATP-competitive and selective inhibitor of Akt2 with IC50 of 6 nM in a cell-free assay, 28-fold greater selectivity for Akt2 than the closely related PKA kinase. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. High dose of CCT128930 triggers cell apoptosis in HepG2 cells.
ACS Nano, 2021, 10.1021/acsnano.1c06452
Front Pharmacol, 2020, 11:593832
Biomed Pharmacother, 2020, 130:110544
S2658 Omipalisib (GSK2126458) Omipalisib (GSK2126458, GSK458) is a highly selective and potent inhibitor of p110α/β/δ/γ, mTORC1/2 with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM in cell-free assays, respectively. Omipalisib induces autophagy. Phase 1.
Cell Metab, 2021, S1550-4131(21)00326-0
Cancer Res, 2021, canres.3199.2020
Mol Cancer Res, 2021, molcanres.0301.2021
S2673 Trametinib (GSK1120212) Trametinib (GSK1120212, JTP-74057, Mekinist) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis.
Nature, 2021, 10.1038/s41586-021-03916-2
Cell, 2021, 184(25):6119-6137.e26
Nat Biotechnol, 2021, 10.1038/s41587-021-00837-3
S2679 Flavopiridol (L86-8275) HCl Flavopiridol HCl (L86-8275, NSC 649890, Alvocidib, HMR-1275, DSP-2033) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM in cell-free assays. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol HCl induces autophagy and ER stress. Flavopiridol HCl blocks HIV-1 replication. Phase 1/2.
Nature, 2021, 10.1038/s41586-021-03445-y
Genome Res, 2021, 31(6):981-994
EMBO Rep, 2021, e52023
S2696 Apitolisib (GDC-0980) Apitolisib (GDC-0980, RG7422, GNE 390) is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively. Also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases. Apitolisib activates autophagy and apoptosis simultaneously in pancreatic cancer cells. Phase 2.
Adv Sci (Weinh), 2021, e2103360
Cancers (Basel), 2021, 13(9)2139
Commun Biol, 2021, 4(1):1333
S2713 Geldanamycin (NSC 122750) Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.
Cell Chem Biol, 2021, S2451-9456(21)00221-X
J Virol, 2021, JVI0059421
Int J Pharm, 2021, 610:121272
S2751 Milciclib (PHA-848125) Milciclib (PHA-848125) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Milciclib (PHA-848125) induces cell death through autophagy. Phase 2.
Sci Rep, 2021, 11(1):7259
Eur J Pharm Sci, 2021, 159:105740
Eur J Pharm Sci, 2021, S0928-0987(21)00042-7
S2770 MK-5108 (VX-689) MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) induces autophagy. Phase 1.
Cancer Cell, 2021, S1535-6108(21)00383-4
Adv Sci (Weinh), 2021, e2103360
Anal Chem, 2021, 93(30):10653-10660
S2782 GW4064 GW4064 is an agonist of farnesoid X receptor (FXR) with EC50 of 65 nM in CV1 cell line and displays no activity at other nuclear receptors at concentrations up to 1 μM. GW4064 stimulates autophagy in MCF-7 cells.
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Theranostics, 2020, 10(23):10434-10447
J Neuroinflammation, 2020, 25;17(1):164
S2783 Vistusertib (AZD2014) Vistusertib (AZD2014) is a novel mTOR inhibitor with IC50 of 2.8 nM in a cell-free assay; highly selective against multiple PI3K isoforms (α/β/γ/δ). AZD2014 showed no or weak binding to the majority of kinases when tested at 1 μM. AZD2014 induces proliferation suppression, apoptosis, cell cycle arrest, and autophagy in HCC cells with antitumor activity.
Adv Sci (Weinh), 2021, e2103360
Nat Commun, 2021, 12(1):1876
Cell Rep, 2021, 35(1):108940
S2799 Daporinad (FK866, APO866) Daporinad (FK866, APO866) effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase; Nampt) with IC50 of 0.09 nM in a cell-free assay. Daporinad (FK866, APO866) triggers autophagy. Phase 1/2.
Cancer Cell, 2021, S1535-6108(21)00338-X
Cell Metab, 2021, 33(1):110-127.e5
Free Radic Biol Med, 2021, 162:514-522
S2812 (R)-(-)-Gossypol acetic acid (R)-(-)-Gossypol (AT-101) acetic acid, the R-(-) enantiomer of Gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.32 μM, 0.48 μM and 0.18 μM in cell-free assays; does not inhibit BIR3 domain and BID. AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy. Phase 2.
Eur J Pharm Sci, 2020, 142:105105
Platelets, 2020, 10.1080/09537104.2020.1724276
Cancers (Basel), 2020, 12(8):E2298
S2817 Torin 2 Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis.
Nat Commun, 2021, 12(1):245
Cell Rep, 2021, 35(1):108940
Cell Death Dis, 2021, 12(11):1028
S2827 Torin 1 Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.
Cell Metab, 2021, S1550-4131(21)00326-0
Mol Cell, 2021, S1097-2765(21)00736-X
Nat Commun, 2021, 12(1):4789
S2843 BI-D1870 BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. BI-D1870 exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.
EMBO J, 2021, 40(7):e106106
Cell Rep, 2021, 37(12):110137
J Med Chem, 2021, 64(18):13572-13587
S2853 Carfilzomib (PR-171) Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis.
Cancer Cell, 2021, S1535-6108(20)30609-7
Sci Adv, 2021, 7(23)eabg2697
Autophagy, 2021, 1-14
S2929 Pifithrin-α (PFTα) HBr Pifithrin-α is an inhibitor of p53, inhibiting p53-dependent transactivation of p53-responsive genes. Pifithrin-α is also a potent agonist of the aryl hydrocarbon receptor (AhR).
Br J Pharmacol, 2021, 10.1111/bph.15385
Development, 2021, dev.188276
Biochim Biophys Acta Mol Cell Res, 2021, 1869(2):119174
S3012 Pazopanib Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces cathepsin B activation and autophagy.
Cancer Res, 2021, canres.1222.2021
Cancers (Basel), 2021, 13(14)3635
Radiother Oncol, 2021, 157:175-181
S3017 Aspirin (NSC 27223) Aspirin (NSC 27223, Acetylsalicylic acid, ASA) is a salicylate, and irreversible COX1 and COX2 inhibitor, used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. Aspirin induces autophagy and stimulates mitophagy.
Dev Cell, 2021, S1534-5807(21)00485-8
Pigment Cell Melanoma Res, 2021, 10.1111/pcmr.13021
Int Immunopharmacol, 2021, 95:107558
S3022 Cabazitaxel (XRP6258) Cabazitaxel (RPR-116258A, XRP6258, TXD 258, Taxoid XRP6258) is a semi-synthetic derivative of a natural taxoid that kills cancer cells by inhibiting cell division and growth. Cabazitaxel exerts its effects by inhibiting microtubule growth and assembly, processes that are essential for cells to divide. Cabazitaxel induces autophagy via the PI3K/Akt/mTOR pathway.
Mol Cancer Ther, 2021, molcanther.0983.2020
Prostate, 2021, 10.1002/pros.24138
Prostate, 2021, 10.1002/pros.24200
S3030 Niclosamide (BAY2353) Niclosamide (BAY2353, Niclocide, NSC 178296) can inhibit DNA replication and inhibit STAT3 with IC50 of 0.7 μM in a cell-free assay. Niclosamide selectively inhibited the phosphorylation of STAT3 and had no obvious inhibition against the activation of other homologues (e.g., STAT1 and STAT5).
Cell Death Differ, 2021, 10.1038/s41418-021-00781-4
Cell Death Dis, 2021, 12(9):799
Biochim Biophys Acta Mol Cell Res, 2021, 1868(10):119080
S3031 Linagliptin (BI-1356) Linagliptin (BI-1356) is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM and exhibits a 10,000-fold higher selectivity for DPP-4 than for other dipeptidyl peptidases such as DPP-2, DPP-8, and DPP-9. Linagliptin activates glomerular autophagy in a model of type 2 diabetes. DPP4 mediates ferroptosis in TP53-deficient CRC cells.
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Drug Dev Res, 2021, 10.1002/ddr.21856
S3569New Spermidine Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy.
Int J Mol Sci, 2021, 22(19)10255
Int J Mol Sci, 2021, 22(19), 10255
S3653 Spermidine trihydrochloride Spermidine (4-Azaoctamethylenediamine), a natural polyamine produced from putrescine and decarboxylated S-adenosylmethionine (dcSAM) by spermidine synthase, is a novel autophagy inducer and negatively modulates N-methyl-d-aspartate (NMDA).
Int J Mol Sci, 2021, 22(19)10255
Int J Mol Sci, 2021, 22(19), 10255
S3944 Valproic acid (VPA) Valproic acid (VPA, 2-Propylvaleric Acid, Valproate) is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. It is also a histone deacetylase (HDAC) inhibitor and is under investigation for treatment of HIV and various cancers. Valproic acid (VPA) induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α. Valproic acid activates Notch-1 signaling.
Front Immunol, 2021, 12:771453
Sci China Life Sci, 2021, 10.1007/s11427-020-1855-4
Anticancer Res, 2021, 41(2):687-697
S3984 Nordihydroguaiaretic acid (NDGA) Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It is a recognized inhibitor of lipoxygenase (LOX) and has antioxidant and free radical scavenging properties. Nordihydroguaiaretic acid (NDGA) is a cytotoxic insulin-like growth factor-I receptor (IGF-1R)/HER2 inhibitor and induces apoptosis. Nordihydroguaiaretic acid (NDGA) inhibits p300 and activates autophagy. Nordihydroguaiaretic acid (NDGA) protects cells from ferroptosis.
S4028 Dexamethasone Sodium Phosphate Dexamethasone (Dexamethasone 21-phosphate disodium salt) is a potent synthetic member of the glucocorticoid class of steroid drugs, and an interleukin receptor modulator that has anti-inflammatory and immunosuppressant effects.
Cell Rep, 2021, 36(2):109360
Mol Cancer, 2021, 20(1):84
JCI Insight, 2021, 6(19)e147038
S4081 Sulfacetamide Sodium Sulfacetamide Sodium is an anti-biotic.
G3 (Bethesda), 2020, 4;10(5):1585-1597
S4211 Montelukast Sodium Montelukast (MK-0476) selectively antagonizes leukotriene D4 (LTD4) by binding to it so that block the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1. Montelukast improves macroautophagy but not the chaperone-mediated autophagy pathway. Precipitations may form after reconstitution,solution is best fresh-prepared.
Cancer Immunol Immunother, 2021, 70(1):203-213
CU Digital Repository, 2021, N/A
G3 (Bethesda), 2020, 4;10(5):1585-1597
S4269 Vinorelbine ditartrate (KW-2307) Vinorelbine Tartrate (KW-2307, Nor-5'-anhydrovinblastine ditartrate) is a semi-synthetic vinca alkaloid, and inhibits mitosis through interaction with tubulin. Vinorelbine Tartrate exhibits anti-tumor activities via inducing the mitotic apoptosis, autophagy and inflammation.
Cancer Res, 2021, canres.0955.2021
Br J Cancer, 2021, 10.1038/s41416-021-01420-y
J Neurochem, 2021, 156(5):642-657
S4476New PCNA-I1 PCNA-I1 is a selective inhibitor of proliferating cell nuclear antigen (PCNA, a potential anticancer target). PCNA-I1 selectively binds to PCNA trimers with Kd of ~0.2 to 0.4 μM. PCNA-I1 inhibits the growth of tumor cells of various tissue types with IC50 of ~0.2 μM. PCNA-I1 induces DNA damage and apoptosis in both LNCaP and PC-3 cells. PCNA-I1 also induces autophagy in PC-3 cells.
S4505 Vinblastine (NSC-49842) sulfate Vinblastine sulfate (NSC49842, Vincaleukoblastine sulfate salt, 29060-LE, Exal, Velban, Velbe) inhibits microtubule formation and suppresses nAChR activity with IC50 of 8.9 μM in a cell-free assay, used to treat certain kinds of cancer. Vinblastine sulfate induces autophagy and apoptosis.
Nat Chem Biol, 2021, 10.1038/s41589-021-00751-4
Cancer Res, 2021, canres.0955.2021
Hum Cell, 2021, 10.1007/s13577-021-00579-z
S4546 Xylitol Xylitol (Adonitol, Ribitol, Xylite, D-Xylitol, Adonite) is a sugar alcohol derived from XYLOSE by reduction of the carbonyl group. It is as sweet as sucrose and used as a noncariogenic sweetener.
S4613New Sodium Fluoride Sodium fluoride (NaF) induces apoptosis and autophagy via the endoplasmic reticulum (ER) stress pathway in MC3T3-E1 osteoblastic cells.
S4908 SN-38 SN-38 (NK012) is an active metabolite of CPT-11, inhibits DNA topoisomerase I, DNA synthesis and causes frequent DNA single-strand breaks. SN-38 induces autophagy.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Sci Transl Med, 2021, 13(622):eabb5445
S5003 Tacrolimus (FK506) Tacrolimus (FK506, FR900506, Fujimycin, Prograf) is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. Tacrolimus also inhibits the phosphatase activity of calcineurin. Tacrolimus induces vascular endothelial autophagy.
EMBO Mol Med, 2021, 13(3):e12834
Cell Mol Gastroenterol Hepatol, 2021, S2352-345X(21)00135-1
PLoS Biol, 2021, 19(5):e3001263
S5243 Ruxolitinib Phosphate Ruxolitinib Phosphate (INCB018424, INC424) is the phosphate salt form of Ruxolitinib. Ruxolitinib is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Sci Immunol, 2021, 6(59)eabi9007
Nat Commun, 2021, 12(1):7268
J Cell Biol, 2021, 220(9)e202004114
S5248 Apatinib Apatinib (Rivoceranib, YN968D1) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib induces both autophagy and apoptosis.
Biochem Biophys Res Commun, 2021, 586:177-184
Cells, 2020, 9(6):E1452
Cell Death Dis, 2020, 11(3):169
S5554 Lanatoside C Lanatoside C is a cardiac glycoside with antiviral and anti-tumor activity. Lanatoside C induces G2/M cell cycle arrest and induces autophagy and apoptosis via attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR signaling pathways.
S5715 Atorvastatin Atorvastatin is a lipid lowering agent. It is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. Atorvastatin activates autophagy.
Cancers (Basel), 2021, 13(21)5543
Cells, 2021, 10(9)2488
Oncol Lett, 2021, 21(2):82
S5742 Deferoxamine mesylate (Ba 33112) Deferoxamine mesylate (Ba 33112, Desferrioxamine B, DFOM, NSC 644468) is the mesylate salt of Deferoxamine, which forms iron complexes and is used as a chelating agent. Deferoxamine is a ferroptosis inhibitor that stabilizes HIF-1α expression and improves HIF-1α transactivity in hypoxic and hyperglycemic states in vitro. Deferoxamine decreases beta-amyloid (Aβ) deposition and induces autophagy.
Nat Immunol, 2021, 22(9):1107-1117
Nat Commun, 2021, 12(1):647
CHEM ENG J, 2021, 10.1016/j.cej.2021.130083
S6301New MPP+ iodide MPP+ iodide (N-Methyl-4-Phenylpyridinium Iodide), the metabolite of a neurotoxin MPTP, causes symptom of Parkinson's disease (PD) in animal models by selectively destroying dopaminergic neurons in substantia nigra. MPP+ induces autophagic cell death in SH-SY5Y cells. MPP+ induces dopamine transporter (DAT) externalization in dopaminergic (DA) neurons, but internalization of serotonin transporter (SERT) in serotonergic (5-HT) neurons.
S6395New CA77.1 CA77.1 (CA) is a potent, brain-penetrant and orally active activator of chaperone-mediated autophagy (CMA) for the treament of Alzheimer's disease (AD).
S6650 EN6 EN6 is a novel covalent autophagy activator and targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase with an IC50 of 1.7 μM for recombinant human ATP6V1A protein.
Cell Death Dis, 2021, 12(1):119
S6797 QX77 QX77 is a novel activator of chaperone-mediated autophagy (CMA). QX77 induces the up-regulation of Rab11 expression and up-regulates LAMP2A expression.
Front Pharmacol, 2021, 12:707259
S6847 ML-9 HCl ML-9 HCl (ML-9 hydrochloride) is a selective and potent inhibitor of Akt kinase, myosin light chain kinase (MLCK) and stromal interaction molecule 1 (STIM1). ML-9 HCl is also a potent inhibitor of Ca2+-permeable channels. ML-9 HCl is a lysosomotropic agent targeting autophagy and cell death.
J Mol Endocrinol, 2019, 63(3):199-213
S6851 RA-190 RA190, a bis-benzylidine piperidon, is a potent, selective and oral effective inhibitor of proteasome ubiquitin receptor RPN13/ADRM1 with anticancer activity. RA190 triggers ER stress response, p53/p21 signaling axis and autophagy in multiple myeloma cells.
S6919 Brevilin A Brevilin A (6-O-Angeloylplenolina), a sesquiterpene lactone isolated from Centipeda minima, is a selective inhibitor of STAT3 and attenuates the JAKs activity by blocking the JAKs tyrosine kinase domain JH1. Brevilin A induces apoptosis and autophagy of colon adenocarcinoma cell CT26 via mitochondrial pathway and PI3K/AKT/mTOR inactivation.
S6957 β-Elemene

β-Elemene ((-)-β-Elemene, Levo-β-elemene) is a sesquiterpene compound extracted from the herb Curcuma Rhizoma with antitumor activities. β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis or autophagy.

S7007 Binimetinib (MEK162) Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3.
Cell, 2021, 184(25):6119-6137.e26
Nat Commun, 2021, 12(1):3707
Neuro Oncol, 2021, 23(5):770-782
S7104 AZD1208 AZD1208 is a potent, and orally available Pim kinase inhibitor with IC50 of 0.4 nM, 5 nM, and 1.9 nM for Pim1, Pim2, and Pim3 in cell-free assays, respectively. AZD1208 induces autophagy, cell cycle arrest and apoptosis. Phase 1.
Cell Rep, 2021, 35(8):109160
Cancers (Basel), 2021, 13(9)2139
FASEB J, 2021, 35(6):e21656
S7106 AZD3463 AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency. AZD3463 suppresses cell viability by inducing both cell apoptosis and autophagy.
Cancers (Basel), 2020, 12(9)E2668
Aging (Albany NY), 2020, 7;12(9):8221-8240
Burns Trauma, 2020, 8:tkaa025
S7110 (+)-JQ1 (+)-JQ1 is a BET bromodomain inhibitor, with IC50 of 77 nM/33 nM for BRD4(1/2) in cell-free assays, binding to all bromodomains of the BET family, but not to bromodomains outside the BET family. (+)-JQ1 suppresses cell proliferation via inducing autophagy. (+)-JQ1 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.
Cell, 2021, S0092-8674(21)00354-8
Cell, 2021, 184(25):6119-6137.e26
Mol Cell, 2021, S1097-2765(21)00995-3
S7130 PR-619 PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 activates autophagy.
Mol Cell, 2021, S1097-2765(21)00800-5
Nat Commun, 2021, 12(1):2970
Nat Commun, 2021, 12(1):5263
S7134 IU1 IU1 is a cell-permeable, reversible and selective proteasome inhibitor of human USP14 with IC50 of 4.7 μ M, 25-fold selective to IsoT. IU1 induces autophagy.
Cell Death Dis, 2021, 12(9):803
FASEB J, 2021, 35(9):e21870
Cell Chem Biol, 2021, S2451-9456(21)00213-0
S7152 C646 C646 is an inhibitor for histone acetyltransferase, and inhibits p300 with a Ki of 400 nM in a cell-free assay. Preferentially selective for p300 versus other acetyltransferases. C646 induces cell cycle arrest, apoptosis and autophagy.
Hepatology, 2021, 10.1002/hep.32245
Cancer Lett, 2021, 513:36-49
Cancer Lett, 2021, S0304-3835(21)00532-2
S7164 GSK343 GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.
Hepatology, 2021, 10.1002/hep.32245
Nat Commun, 2021, 12(1):4147
Proc Natl Acad Sci U S A, 2021, 118(30)e2102718118
S7165 UNC1999 UNC1999 is a potent, orally bioavailable and selective inhibitor of EZH2 and EZH1 with IC50 of 2 nM and 45 nM in cell-free assays, respectively, showing >1000-fold selectivity over a broad range of epigenetic and non-epigenetic targets. UNC1999 is a potent autophagy inducer. UNC1999 specifically suppresses H3K27me3/2 and induces a range of anti-leukemia effects including anti-proliferation, differentiation, and apoptosis.
Hepatology, 2021, 10.1002/hep.32245
Cancers (Basel), 2021, 13(2)E319
Cancers (Basel), 2021, 13(2)319
S7177 PF-543 PF-543, a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 and Ki of 2.0 nM and 3.6 nM, exhibits >100-fold selectivity over the SphK2 isoform. PF-543 induces apoptosis, necrosis, and autophagy.
J Pharmacol Exp Ther, 2021, 378(3):300-310
Phytother Res, 2021, 10.1002/ptr.7211
Cancer Biol Ther, 2020, 21(9):841-852
S7215 Losmapimod (GW856553X) Losmapimod (GW856553X, GW856553, GSK-AHAB) is a selective, potent, and orally active p38 MAPK inhibitor with pKi of 8.1 and 7.6 for p38α and p38β, respectively. P38 MAPKs are involved in cell differentiation, apoptosis and autophagy. Phase 3.
Free Radic Biol Med, 2021, 167:243-257
Cell, 2020, 182(3):685-712.e19
Cell, 2020, 182(3):685-712.e19
S7306 Dorsomorphin (Compound C) 2HCl Dorsomorphin 2HCl (BML-275, Compound C) is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.
Cell, 2021, 184(2):334-351.e20
Mol Cell, 2021, S1097-2765(21)00232-X
Nat Commun, 2021, 12(1):5058
S7343 URMC-099 URMC-099 is an orally bioavailable, brain penetrant mixed lineage kinase (MLK) inhibitor with IC50 of 19 nM, 42 nM, 14 nM, and 150 nM, for MLK1, MLK2, MLK3, and DLK, respectively, and also inhibits LRRK2 activity with IC50 of 11 nM. URMC-099 also inhibits ABL1 with IC50 of 6.8 nM. URMC-099 induces autophagy.
Cell Rep, 2021, 35(1):108940
JCI Insight, 2021, 149075
Cancer Cell Int, 2021, 21(1):24
S7397 Sorafenib (BAY 43-9006) Sorafenib (BAY 43-9006, NSC-724772) is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
Genome Biol, 2021, 22(1):41
Nat Chem Biol, 2021, 10.1038/s41589-021-00751-4
EMBO Mol Med, 2021, e14351
S7409 Anisomycin Anisomycin (Flagecidin, Wuningmeisu C) is a bacterial antibiotic isolated from Streptomyces griseolus, which inhibits protein synthesis, and also act as a JNK activator. Anisomycin upregulates autophagy and increases apoptosis.
Cell Rep, 2021, 36(7):109515
Acta Neuropathol Commun, 2021, 9(1):169
Int J Mol Sci, 2021, 22(12)6570
S7483 DMOG DMOG (Dimethyloxalylglycine) is an antagonist of α-ketoglutarate cofactor and inhibitor for HIF prolylhydroxylase, leading to stabilisation and accumulation of HIF-1α protein in the nucleus. DMOG enhances autophagy.
Cells, 2021, 10(6)1359
Aging (Albany NY), 2021, 13(8):11705-11726
Cell Prolif, 2021, e13158
S7648 OTS964 OTS964 is a potent TOPK inhibitor with high affinity and selectivity and IC50 value is 28 nM. OTS964 is also a potent inhibitor of the cyclin-dependent kinase CDK11 with Kd of 40 nM. OTS964 treatment activates autophagy in glioma cells and induces apoptosis of human lung cancer cells in mouse xenografts.
Mol Imaging Biol, 2019, 21(4):705-712
S7655 Telaglenastat (CB-839) Telaglenastat (CB-839) is a potent, selective, and orally bioavailable glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC. CB-839(Telaglenastat) inudces autophagy and has antitumor activity. Phase 1.
Cell Metab, 2021, S1550-4131(21)00226-6
Theranostics, 2021, 11(17):8464-8479
Cancer Lett, 2021, 507:80-88
S7680 SP2509 SP2509 (HCI-2509) is a selective histone demethylase LSD1 inhibitor with IC50 of 13 nM, showing no activity against MAO-A, MAO-B, lactate dehydrogenase and glucose oxidase. SP2509 induces apoptosis and promotes autophagy.
Cell Death Dis, 2021, 12(11):993
Front Cell Dev Biol, 2021, 9:694071
Acta Biochim Biophys Sin (Shanghai), 2021, gmab083
S7684 Salirasib Salirasib (Farnesylthiosalicylic acid, FTS) is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with Ki of 2.6 μM, which inhibits Ras methylation. Salirasib exerts antitumor effects and induces autophagy. Salirasib exerts antitumor effects and induces autophagy. Phase 2.
Cancer Manag Res, 2020, 12:2057-2067
Mol Oncol, 2018, 12(2):224-238
Food Chem Toxicol, 2018, 119:464-478
S7724 Eprenetapopt (APR-246) Eprenetapopt (APR-246, PRIMA-1MET) is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell death in various cancer types. APR-246 induces apoptosis and autophagy.
Haematologica, 2021, 10.3324/haematol.2020.259531
Cancers (Basel), 2021, 13(17)4476
Int J Mol Sci, 2021, 22(11)5782
S7781 Sunitinib (SU11248) Sunitinib (SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. Sunitinib is also a dose-dependent inhibitor of the autophosphorylation activity of IRE1α. Sunitinib induces autophagy and apoptosis.
Adv Sci (Weinh), 2021, e2100881
Blood Cancer J, 2021, 11(3):57
Cancers (Basel), 2021, 13(11)2574
S7785 Pemetrexed Disodium Hydrate Pemetrexed Disodium Hydrate (LY-231514) is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM, respectively. Pemetrexed Disodium Hydrate stimulates autophagy and apoptosis.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
J Exp Clin Cancer Res, 2021, 40(1):344
Br J Cancer, 2021, 10.1038/s41416-021-01441-7
S7786 Erlotinib (OSI-774) Erlotinib (OSI-774, CP358774, NSC 718781, Tarceva) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.
Nature, 2021, 595(7869):730-734
Cell, 2021, 184(10):2649-2664.e18
Cancer Cell, 2021, S1535-6108(21)00659-0
S7793 Purvalanol A Purvalanol A is a potent, and cell-permeable CDK inhibitor with IC50 of 4 nM, 70 nM, 35 nM, and 850 nM for cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, and cdk4-cyclin D1, respectively. Purvalanol A induces endoplasmic reticulum stress-mediated apoptosis and autophagy.
Cancer Lett, 2021, 526:53-65
Mol Neurobiol, 2021, 10.1007/s12035-021-02581-w
Aging (Albany NY), 2020, 12(19):19022-19044
S7810 Afatinib (BIBW2992) Dimaleate Afatinib (BIBW2992) Dimaleate irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant. Afatinib (BIBW2992) Dimaleate induces autophagy.
Cancer Cell, 2021, S1535-6108(21)00284-1
Nat Cell Biol, 2021, 23(4):377-390
Clin Cancer Res, 2021, 27(9):2533-2548
S7840 Dorsomorphin (Compound C) Dorsomorphin (Compound C, BML-275) is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For animal testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended.
Cell Res, 2021, 10.1038/s41422-020-00458-6
EMBO Rep, 2021, e51781
J Immunother Cancer, 2021, 9(7)e002844
S7842 LY3009120 LY03009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. LY03009120 induces autophagy. Phase 1.
Nat Cell Biol, 2021, 23(4):377-390
Sci Adv, 2021, 7(24)eabg0390
Nat Commun, 2021, 12(1):7006
S7998 Entrectinib (RXDX-101) Entrectinib (RXDX-101, NMS-E628) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2.
Nature, 2021, 600(7888):319-323
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
S8006 BIX 01294 BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases. BIX01294 induces autophagy. BIX01294 also inhibits H3K36 methylation by oncoproteins NSD1, NSD2 and NSD3.
Adv Sci (Weinh), 2021, e2100779
Exp Mol Med, 2021, 10.1038/s12276-021-00715-7
Cancer Gene Ther, 2021, 10.1038/s41417-021-00335-3
S8047 Dynasore Dynasore is a cell-permeable, reversible non-competitive dynamin inhibitor of GTPase activity of dynamin 1/2, with IC50 of 15 μM in a cell-free assay, also inhibits the mitochondrial dynamin Drp1, with no effect against other small GTPase. Dynasore suppresses mTORC1 activity and induces autophagy. Dynasore inhibits the entry of several viruses, including herpes simplex virus (HSV).
EMBO Rep, 2021, e53185
Theranostics, 2021, 11(5):2364-2380
J Mater Chem B, 2021, 9(11):2641-2655
S8048 Venetoclax (ABT-199) Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Venetoclax is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.
Leukemia, 2021, 10.1038/s41375-021-01347-6
Cell Rep, 2021, 34(11):108870
Cell Death Differ, 2021, 10.1038/s41418-021-00816-w
S8049 Tubastatin A Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
Sci Adv, 2021, 7(49):eabk0490
Sci Adv, 2021, 7(49):eabk0490
Thyroid, 2021, 10.1089/thy.2020.0948
S8059 Nutlin-3a Nutlin-3a ((-)-Nutlin-3), the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM in a cell-free assay. Nutlin-3a induces autophagy and apoptosis in a p53-dependent manner.
PLoS Biol, 2021, 19(8):e3001364
Cell Death Dis, 2021, 12(7):663
Cell Death Dis, 2021, 12(4):364
S8075 GANT61 GANT61 (NSC 136476) is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. GANT61 induces apoptosis and activates protective autophagy in LX-2 cells.
Blood, 2021, blood.2020010207
Elife, 2021, 10e70729
J Bone Miner Res, 2021, 10.1002/jbmr.4265
S8078 Bardoxolone Methyl Bardoxolone Methyl (RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me) is an IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities; Also a potent Nrf2 activator and nuclear factor-κB (NF-κB) inhibitor. Bardoxolone Methyl abrogates ferroptosis. Bardoxolone methyl induces apoptosis and autophagy in cancer cells.
Drug Des Devel Ther, 2021, 15:21-35
Cancers (Basel), 2020, 12(6):E1645
Antioxidants (Basel), 2020, 9(1)
S8240 SMER28 SMER28 is a small-molecule enhancer (SMER) of autophagy, inducing autophagy independently of rapamycin in mammalian cells.
Nat Chem Biol, 2020, 6
Cell Rep, 2020, 31(12):107800
Cell Rep, 2019, 27(12):3413-3421
S8432 Troglitazone (CS-045) Troglitazone (Rezulin, Romglizone, Prelay, CS045, Romozin) is a potent agonist for the peroxisome proliferator-activated receptor-(PPAR) that is a ligand activated transcription factor regulating cell differentiation and growth. Troglitazone induces autophagy, apoptosis and necroptosis in bladder cancer cells. Troglitazone prevents RSL3-induced ferroptosis and lipid peroxidation in Pfa1 cells.
Free Radic Biol Med, 2021, 163:234-242
Biomed Pharmacother, 2020, 132:110741
Nat Commun, 2019, 11;10(1):4621
S8595 Tat-beclin 1 (Tat-BECN1) Tat-beclin 1 (Tat-BECN1), a peptide known to stimulate autophagy through mobilization of endogenous Beclin 1, induces autophagy in vitro and in vivo and improves clinical outcomes.
Autophagy, 2021, 1-16
Cells, 2021, 10(4)898
Eur Rev Med Pharmacol Sci, 2020, 24(18):9246-9255
S8943 VLX600 VLX600 is a novel iron-chelating inhibitor of oxidative phosphorylation (OXPHOS), potentiates the effect of radiation in tumor spheroids in a synergistic manner. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. VLX600 induces autophagy and mitochondrial inhibition with antitumor activity.
S9027 Corynoxine Corynoxine, a natural oxindole alkaloid, is a new autophagy enhancer.
S9310 Isorhychophylline Isorhynchophylline (IsoRhy, 7-Isorhyncophylline) is a major tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.)Jacks (Gouteng in Chinese). It acts as a neuronal autophagy inducer with therapeutic potential for cardiovascular and central nervous system diseases.
S9611 ABTL-0812 ABTL0812 (α-Hydroxylinoleic acid, LP-10218, SCLN-0812) inhibits Akt/mTOR axis by inducing the overexpression of TRIB3 and activating autophagy in lung squamous carcinoma cell lines. ABTL0812 also induces AMPK activation and ROS accumulation.
S9860New BC1618 BC1618 is an orally active Fbxo48 inhibitor that stimulates adenosine monophosphate (AMP)-activated protein kinase (Ampk)-dependent signaling. BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity.
S7307 GSK2606414 GSK2606414 is an orally available, potent, and selective PERK inhibitor with IC50 of 0.4 nM, displaying at least 100-fold selectivity over the other EIF2AKs assayed. GSK2606414 impairs GANT-61 induced autophagy in NB cells with MYCN amplification. GSK2606414 exacerbates ER stress-induced apoptosis in HCT116 cells while reduces the apoptosis in SIL1 KD HeLa cells.
EMBO Mol Med, 2021, e14502
Autophagy, 2021, 1-21
Free Radic Biol Med, 2021, S0891-5849(21)00773-5
S5973New Methylprednisolone Acetate Methylprednisolone (NSC-19987, Medrol) acetate is a synthetic glucocorticoid receptor agonist, used to achieve prompt suppression of inflammation. Methylprednisolone activates ACE2 and reduces IL-6 levels, thus improves severe or critical COVID-19. Methylprednisolone markedly reduces autophagy and apoptosis.
S8597 LYN-1604 LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanomole range (Kd=291.4 nM). The ULK1 (Y89A) mutant protein caused a sharp decrease in binding affinity with lower response and Kd than wild-type ULK1, ULK1 (K50A) and ULK1 (L53A) mutants.
J Virol, 2021, JVI0155021
Exp Eye Res, 2019, 184:126-134
S1041 STF-62247 STF-62247 is a molecule targeting VHL-deficient renal cell carcinoma that induces autophagy. STF-62247 shows selective toxicity and growth inhibition of renal cells lacking VHL; 25-fold greater sensitivity observed for cells with VHL deficiency compared to wild-type (VHL+).
Neuropsychiatr Dis Treat, 2015, 11:2091-9
S1204 Melatonin (NSC 113928) Melatonin (NSC 113928, NSC 56423, N-Acetyl-5-methoxytryptamine) is a MT receptor agonist, used as a dietary supplement. Melatonin is a selective ATF-6 inhibitor and downregulates COX-2. Melatonin enhances mitophagy and regulates the homeostasis of apoptosis and autophagy.
Cell Chem Biol, 2021, S2451-9456(21)00442-6
Int J Mol Sci, 2021, 22(11)5649
Int Immunopharmacol, 2021, 96:107787
S1241 Vincristine (NSC-67574) sulfate Vincristine sulfate (NSC-67574, Leurocristine, Oncovin, 22-Oxovincaleukoblastine) is an inhibitor of polymerization of microtubules by binding to tubulin with IC50 of 32 μM in a cell-free assay. Vincristine sulfate induces apoptosis.
Theranostics, 2021, 11(9):4281-4297
Cell Rep, 2021, 36(11):109718
Cell Rep, 2021, 35(13):109302
S1274 BX-795 BX-795 is a potent and specific PDK1 inhibitor with IC50 of 6 nM, 140- and 1600-fold more selective for PDK1 than PKA and PKC in cell-free assays, respectively. Meanwhile, in comparison to GSK3β more than 100-fold selectivity observed for PDK1. BX-795 modulates autophagy via inhibiting ULK1. BX-795 also is a potent TBK1 inhibitor that blocks both TBK1 and IKKε with IC 50 values of 6 nM and 41 nM, respectively.
Immunity, 2021, S1074-7613(21)00069-8
Nat Commun, 2021, 12(1):5401
J Immunother Cancer, 2021, 9(10)e003050
S1627 Nitazoxanide (NSC 697855) Nitazoxanide (NTZ, NSC 697855) is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent(IC50 for canine influenza virus ranges from 0.17 to 0.21 μM). Nitazoxanide modulates autophagy and inhibits mTORC1 signaling.
Heliyon, 2021, 7(7):e07586
Biomedicines, 2021, 9(8)949
Biomed J, 2020, S2319-4170(20)30066-4
S2215 DAPT (GSI-IX) DAPT (GSI-IX, LY-374973) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. DAPT enhances the apoptosis of human tongue carcinoma cells and regulates autophagy.
Immunity, 2021, S1074-7613(21)00344-7
Neuron, 2021, 109(12):1949-1962.e6
Sci Adv, 2021, 7(5)eabc9781
S2271 Berberine chloride (NSC 646666) Berberine chloride (NSC 646666, Natural Yellow 18) is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator.
Front Pharmacol, 2021, 12:632201
Molecules, 2021, 26(5)1210
Biology (Basel), 2021, 10(3)250
S2924 CHIR-99021 (CT99021) HCl CHIR-99021 (CT99021) HCl is hydrochloride of CHIR-99021, which is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs Cdc2 and ERK2. CHIR-99021 is a potent pharmacological activators of the Wnt/beta-catenin signaling pathway. CHIR-99021 significantly rescues light-induced autophagy and augments GR, RORα and autophagy-related proteins.
Nat Genet, 2021, 53(12):1686-1697
Nat Genet, 2021, 53(4):467-476
Eur Heart J, 2021, ehab547
S5144 Neferine Neferine ((R)-1,2-Dimethoxyaporphine), a natural component of Nelumbo nucifera, has antitumor efficiency. Neferine induces apoptosis in renal cancer cells. Neferine prevents autophagy through activation of Akt/mTOR pathway and Nrf2 in muscle cells. Neferine strongly inhibits NF-κB activation. Neferine possesses a number of therapeutic effects such as anti-diabetic, anti-aging, anti-microbial, anti-thrombotic, anti-arrhythmic, anti-inflammatory and even anti-HIV.
Oncol Rep, 2020, 44(3):1116-1126
S6889 Monomethyl Fumarate Monomethyl Fumarate (MMF, Monomethylfumarate, Fumaric acid monomethyl ester, Methyl hydrogen fumarate), the active metabolite of the psoriasis drug Fumaderm, is a potent GPR109A agonist. Monomethyl Fumarate prevents major dysfunctions associated with neurodegenerative diseases: oxidative stress, mitochondrial dysfunction, apoptosis and autophagy.
Aging (Albany NY), 2021, 13(13):17097-17117
S7153 10058-F4 10058-F4 is a c-Myc inhibitor that specificallly inhibits the c-Myc-Max interaction and prevents transactivation of c-Myc target gene expression. 10058-F4 promotes a caspase-3-dependent apoptosis and modulates autophagy.
J Immunother Cancer, 2021, 9(7)e002528
Cancer Res, 2021, canres.1023.2021
Redox Biol, 2021, 39:101811
S7980 VPS34-IN1 Vps34-IN1 is a potent and highly selective Vps34 inhibitor with IC50 of 25 nM invitro,which does not significantly inhibit the isoforms of class I as well as class II PI3Ks. Vps34-IN1 modulates autophagy.
Nat Genet, 2021, 53(4):435-444
Cell Rep, 2021, 35(1):108940
Sci Rep, 2021, 11(1):9011
S4750 Sulfacetamide sodium salt hydrate Sulfacetamide is a sulfonamide antibiotic that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase(DHPS) with IC50 of 9.5 μM. Sulfacetamide is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), which is required for bacterial synthesis of folic acid.
S1013 Bortezomib (PS-341) Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.
J Cell Biol, 2022, 221(1)e202103033
Nature, 2021, 10.1038/s41586-020-03118-2
Nat Cell Biol, 2021, 10.1038/s41556-021-00766-y
S1092 KU-55933 (ATM Kinase Inhibitor) KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy.
Nat Genet, 2021, 10.1038/s41588-021-00893-0
Cancer Cell, 2021, S1535-6108(20)30658-9
Sci Transl Med, 2021, 13(622):eabb5445
S1102 U0126-EtOH U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. U0126 inhibits autophagy and mitophagy with antiviral activity.
J Am Chem Soc, 2021, 10.1021/jacs.1c05386
Sci Adv, 2021, 7(36):eabi9787
Theranostics, 2021, 11(3):996-1015
S1105 LY294002 LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
Biomed Pharmacother, 2022, 145:112437
Immunity, 2021, S1074-7613(21)00069-8
Immunity, 2021, S1074-7613(21)00403-9
S1109 BI 2536 BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
Nat Commun, 2021, 12(1):5356
Proc Natl Acad Sci U S A, 2021, 118(34)e2108145118
S1113 GSK690693 GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. GSK690693 also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively. GSK690693 affects Unc-51-like autophagy activating kinase 1 (ULK1) activity, robustly inhibits STING-dependent IRF3 activation. Phase 1.
Oncogene, 2021, 10.1038/s41388-021-01932-0
Breast Cancer Res, 2021, 23(1):81
Cancer Discov, 2021, candisc.1265.2020
S1150 Paclitaxel (NSC 125973) Paclitaxel (NSC 125973, PTX, Taxol, Onxal, Abraxane) is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancer Cell, 2021, S1535-6108(20)30658-9
S1346 Heparin sodium Heparin sodium, a sulfated polysaccharide belonging to the family of glycosaminoglycans, has numerous important biological activities associated with its interaction with diverse proteins. Heparin is used as an anticoagulant primarily through its interaction with AT III by enhancing AT-IIImediated inhibition of blood coagulation factors, including thrombin and factor Xa. Heparin prevents the induction of autophagy.
J Extracell Vesicles, 2021, 10(8):e12091
Nat Struct Mol Biol, 2021, 10.1038/s41594-020-00537-7
Theranostics, 2021, 11(5):2364-2380
S1413 Bafilomycin A1 (Baf-A1) Bafilomycin A1(Baf-A1) is a vacuolar H+-ATPase inhibitor with IC50 of 0.44 nM. Bafilomycin A1 is found to inhibit autophagy while induces apoptosis.
Adv Sci (Weinh), 2021, e2100779
Mol Cell, 2021, S1097-2765(21)00729-2
ACS Nano, 2021, 10.1021/acsnano.1c06452
S1460 SP600125 SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase AFLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis.
Biomed Pharmacother, 2022, 145:112437
Immunity, 2021, S1074-7613(21)00403-9
Immunity, 2021, S1074-7613(21)00210-7
S1490 Ponatinib (AP24534) Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy.
J Ethnopharmacol, 2022, 283:114667
Acta Neuropathol, 2021, 10.1007/s00401-021-02327-x
Mol Syst Biol, 2021, 17(9):e10426
S1733 Methylprednisolone (NSC-19987) Methylprednisolone (NSC-19987) is a synthetic glucocorticoid receptor agonist, used to achieve prompt suppression of inflammation. Methylprednisolone activates ACE2 and reduces IL-6 levels, thus improves severe or critical COVID-19. Methylprednisolone markedly reduces autophagy and apoptosis.
Drug Test Anal, 2020, 10.1002/dta.2917
Nat Med, 2017, 23(4):424-428
Trop J Pharm Res, 2014, 13 (1): 53-59
S1786 Verteporfin (CL 318952) Verteporfin (CL 318952, Visudyne) is a small molecule that inhibits TEAD–YAP association and YAP-induced liver overgrowth. It is also a potent second-generation photosensitizing agent derived from porphyrin. Verteporfin is an autophagy inhibitor. Verteporfin inhibits cell proliferation and induces apoptosis.
Nature, 2021, 10.1038/s41586-021-04267-8
Cell Res, 2021, 10.1038/s41422-021-00477-x
Nat Commun, 2021, 12(1):3055
S1835 Azithromycin (CP-62993) Azithromycin (CP-62993, XZ-450) is an antibiotic by inhibiting protein synthesis, used for the treatment of bacterial infections.
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Biomolecules, 2020, 10(10)E1395
S2243 Degrasyn (WP1130) Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT). Degrasyn (WP1130) induces apoptosis and blocks autophagy.
Br J Cancer, 2021, 10.1038/s41416-021-01421-x
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Transl Lung Cancer Res, 2021, 10(10):3995-4011
S2704 LY2109761 LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2. LY2109761 blocks autophagy and induces apoptosis.
Nat Commun, 2021, 12(1):2102
Nucleic Acids Res, 2021, 49(22):12855-12869
Cell Rep, 2021, 34(12):108882
S2758 Wortmannin (KY 12420) Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Adv Sci (Weinh), 2021, e2004303
J Extracell Vesicles, 2021, 10(8):e12091
J Am Chem Soc, 2021, 10.1021/jacs.1c05386
S2767 3-Methyladenine (3-MA) 3-Methyladenine (3-MA, NSC 66389) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation. 3-Methyladenine (3-MA) is successfully used to suppress mitophagy. Solutions of 3-MA are best fresh-prepared by heating.
Bone, 2022, 154:116262
Cell Host Microbe, 2021, S1931-3128(21)00192-X
Nat Commun, 2021, 12(1):4794
S2775 Nocodazole (R17934) Nocodazole (R17934, Oncodazole, NSC238159) is a rapidly-reversible inhibitor of microtubule polymerization, also inhibits Abl, Abl(E255K) and Abl(T315I) with IC50 of 0.21 μM, 0.53 μM and 0.64 μM in cell-free assays, respectively. Nocodazole induces apoptosis.
Cancer Cell, 2021, S1535-6108(21)00383-4
Mol Cell, 2021, S1097-2765(21)00736-X
Nat Commun, 2021, 12(1):5977
S2930 Pifithrin-μ Pifithrin-μ (NSC 303580, PFTμ, 2-Phenylethynesulfonamide) is a specific p53 inhibitor by reducing its affinity to Bcl-xL and Bcl-2, and also inhibits HSP70 function and autophagy.
Shock, 2021, 55(1):74-82
Radiat Res, 2020, 193(2):119-129
Clin Transl Med, 2020, 10.1002/ctm2.41
S3042 Purmorphamine Purmorphamine (Shh Signaling Antagonist VI), which directly binds and activates Smoothened, blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM in HEK293T cell and also is an inducer of osteoblast differentiation with EC50 of 1 μM. Purmorphamine can reduce both basal and induced autophagy.
Cancer Cell, 2021, 39(3):407-422.e13
Front Cell Dev Biol, 2021, 9:679806
Can J Physiol Pharmacol, 2021, 10.1139/cjpp-2020-0588
S3233 Emetine hydrochloride Emetine hydrochloride (NSC 33669), a principal alkaloid extracted from the root of ipecac clinically used as an emetic and antiprotozoal drug, reduces HIFs (hypoxia-inducible factors; HIF-1α and HIF-2α), PDK1, RhoA, Rho-kinases (ROCK1 and ROCK2) and BRD4. Emetine hydrochloride inhibits cellular autophagy and has anti-malarial, anti-viral, anti-bacterial and anti-amoebic effect.
S3592New 4-Phenylbutyric acid (4-PBA) 4-Phenylbutyric acid (4-PBA, Benzenebutyric acid) is a histone deacetylase (HDAC) inhibitor and a key epigenetic inducer of anti-HCV hepatic hepcidin. 4-Phenylbutyric acid inhibits LPS-induced inflammation through regulating endoplasmic-reticulum (ER) stress and autophagy in acute lung injury models.
Toxicol In Vitro, 2021, 77:105249
Nan Fang Yi Ke Da Xue Xue Bao, 2021, 41(5):702-709
Part Fibre Toxicol, 2020, 17(1):50
S3758 Sinomenine hydrochloride Sinomenine (SN, Cucoline, Kukoline, Sabianine A), extracted from the Chinese medicinal plant, sinomenium acutum, is a potent anti-inflammatory and neuroprotective agent.
Cancer Manag Res, 2021, 13:1189-1204
Bioorg Med Chem, 2020, 31:115986
S4157 Chloroquine diphosphate Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator. Chloroquine is also an inhibitor of toll-like receptors (TLRs).
Bone, 2022, 154:116262
Cancer Cell, 2021, S1535-6108(21)00659-0
Gut, 2021, 70(5):890-899
S4430 Hydroxychloroquine Sulfate (NSC 4375) Hydroxychloroquine Sulfate (NSC 4375, HCQ) is an antimalarial agent used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune, inflammatory and dermatologic conditions. Also acts as an inhibitor of autophagy and toll-like receptor (TLR) 7/9.
Autophagy, 2021, 1-14
EMBO Mol Med, 2021, 13(9):e13193
Cell Rep, 2021, 35(1):108940
S4484New Trametinib DMSO solvate Trametinib (GSK1120212, JTP-74057, Mekinist) DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis.
S4643New KB-R7943 mesylate KB-R7943 mesylate is a widely used inhibitor of the reverse Na+/Ca2+ exchanger (NCX(rev)) with IC50 of 5.7 μM. KB-R7943 mesylate promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux.
S4895New Nilotinib hydrochloride monohydrate Nilotinib (AMN-107, Tasigna) hydrochloride monohydrate is a selective and orally bioavailable inhibitor of Bcr-Abl with IC50 < 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
EMBO Mol Med, 2021, e11814
Mol Metab, 2021, 55:101410
Cancers (Basel), 2021, 13(21)5543
S5190New Crizotinib hydrochloride Crizotinib (PF-02341066) hydrochloride (Xalkori) inhibits tyrosine phosphorylation of c-Met and nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) with IC50 of of 11 nM and 24 nM in cell-based assays, respectively. Crizotinib hydrochloride is also a potent ROS1 inhibitor with Ki less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Nature, 2021, 600(7888):319-323
Nat Commun, 2021, 12(1):5006
Cancer Res, 2021, 81(23):5935-5947
S5920 CA-5f CA-5f is a potent late-stage macroautophagy/autophagy inhibitor via inhibiting autophagosome-lysosome fusion.
J Virol, 2021, JVI0155021
S5971New Pemetrexed Pemetrexed (LY231514, Alimta) is a novel antifolate and antimetabolite for thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT) with Ki of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.
J Exp Clin Cancer Res, 2021, 40(1):344
Br J Cancer, 2021, 10.1038/s41416-021-01441-7
Front Oncol, 2021, 11:711043
S6078New ICCB-19 hydrochloride ICCB-19 hydrochloride is an inhibitor of TNFRSF1A Associated Via Death Domain (TRADD) with IC50 of 1.12 μM and 2.01 μM for protecting Velcade-induced apoptosis in Jurkat cells and protecting RDA in MEFs, respectively. ICCB-19 indirectly inhibits Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). ICCB-19 effectively induces autophagy.
S6471 Lucanthone Lucanthone is a novel autophagic inhibitor and also an orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1.
S6716 NSC 185058 NSC185058 inhibits ATG4B, the lipidation of LC3B, and autophagy without affecting the MTOR or PtdIns3K pathways.
S6912 Vacuolin-1 Vacuolin-1 is a potent and cell-permeable inhibitor that blocks the Ca(2+)-dependent exocytosis of lysosomes and prevents the release of lysosomal content without affecting the process of resealing. Vacuolin-1 is also a potent and selective PIKfyve inhibitor, and inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition.
S6999New Chloroquine (NSC-187208) Chloroquine (NSC-187208, Aralen, CHQ, CQ) is an antimalarial drug and autophagy/lysosome inhibitor. Chloroquine also suppresses Toll-like receptor-9 (TLR9) protein expression. Chloroquine is highly effective agianst SARS-CoV-2 (COVID-19) infection with EC50 of 1.13 μM in Vero E6 cells. Chloroquine has anti-HIV-1 activity.
Bone, 2022, 154:116262
Dev Cell, 2021, 56(16):2313-2328.e7
Autophagy, 2021, 10.1080/15548627.2021.1912270
S7033 GSK2656157 GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases apoptosis and inhibits excessive autophagy.
Neurobiol Dis, 2021, 156:105407
Cell Death Dis, 2020, 11(2):125
Sci Rep, 2020, 10(1):9666
S7046 Brefeldin A Brefeldin A is a lactone antibiotic and ATPase inhibitor for protein transport with IC50 of 0.2 μM in HCT 116 cells, induces cancer cell differentiation and apoptosis. It could also improve the HDR(homology-directed repair) efficiency and be an enhancer of CRISPR-mediated HDR. Brefeldin A is also an inhibitor of autophagy and mitophagy.
Nat Cell Biol, 2021, 10.1038/s41556-021-00704-y
Nat Biomed Eng, 2021, 10.1038/s41551-020-00675-9
Cell Rep, 2021, 36(6):109516
S7146 DMH1 DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. DMH1 inhibits autophagy.
Nat Commun, 2021, 12(1):6374
Proc Natl Acad Sci U S A, 2021, 118(29)e2101783118
Cell Rep, 2021, 34(12):108889
S7289 PFK15 PFK15 (PFK-015) is a potent and selective 6-phosphofructo-2-kinase (PFKFB3) inhibitor with IC50 of 207 nM.
Autophagy, 2021, 1-19
Front Immunol, 2021, 12:669456
J Am Heart Assoc, 2021, 10(17):e020231
S7381 Pepstatin A Pepstatin A (Pepstatin) is a potent aspartic protease inhibitor, and also inhibits HIV replication. Pepstatin A is also an inhibitor of cathepsins D and cathepsins E. Pepstatin A inhibits autophagy by suppressing lysosomal proteases.
Pharmacol Res, 2021, S1043-6618(21)00517-X
J Virol, 2021, JVI0155021
Acta Pharmacol Sin, 2021, 10.1038/s41401-021-00768-4
S7423 KN-93 Phosphate KN-93 Phosphate is a potent and specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with Ki of 0.37 μM, no remarkable inhibitory effects on APK, PKC, MLCK or Ca2+-PDE activities. KN-93 attenuates CaMKII-induced autophagy.
Cell Rep, 2021, 35(11):109238
Autophagy, 2021, 1-19
Cell Mol Gastroenterol Hepatol, 2021, S2352-345X(21)00135-1
S7455 Resatorvid (TAK-242) Resatorvid (TAK-242, CLI-095) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling, blocking LPS-induced production of NO, TNF-α and IL-6 in macrophages with IC50 of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy.
FASEB J, 2021, 35(4):e21485
Int J Biol Macromol, 2021, 183:145-157
Front Pharmacol, 2021, 12:626949
S7660 Obeticholic Acid Obeticholic Acid (INT-747, 6-ECDCA, 6-Ethylchenodeoxycholic acid) is a potent and selective farnesoid X receptor (FXR) agonist with EC50 of 99 nM. Obeticholic Acid inhibits autophagy. Phase 3.
Nutrients, 2021, 13(3)940
Proc Natl Acad Sci U S A, 2020, 117(45):28263-28274
Nat Metab, 2020, 2(5):413-431
S7682 SAR405 SAR405 is a low-molecular-mass kinase inhibitor of PIK3C3/Vps34 (KD 1.5 nM) showing high selectivity and not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. SAR405 prevents autophagy and synergizes with MTOR (mechanistic target of rapamycin) inhibition in tumor cells.
Autophagy, 2021, 1-18
Autophagy, 2021, 1-16
Cell Death Dis, 2021, 12(11):1028
S7683 PIK-III PIK-III (VPS34-IN2), which is a selective inhibitor of ​VPS34 enzymatic activity, inhibits autophagy and de novo lipidation of LC3 and leads to the stabilization of autophagy substrates. The IC50 values for VPS34 and PI(3)Kδ are 0.018 μM and 1.2 μM respectively.
Sci Adv, 2021, 7(40):eabj2485
Oxid Med Cell Longev, 2021, 2021:7654143
Nature, 2020, 10.1038/s41586-020-03056-z
S7751 VER155008 VER155008 (C07) is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.
EMBO J, 2021, e106183
Oncogene, 2021, 10.1038/s41388-021-01914-2
Eur J Med Chem, 2021, 220:113452
S7811 MHY1485 MHY1485 is a potent, and cell-permeable mTOR activator, and also potently inhibits autophagy.
Nat Commun, 2021, 12(1):1736
Cell Rep, 2021, 36(5):109490
Cells, 2021, 10(3)558
S7885 SBI-0206965 SBI-0206965 is a highly selective autophagy kinase ULK1 inhibitor with IC50 of 108 nM, about 7-fold selectivity over ULK2. SBI-0206965 inhibits autophagy and enhances apoptosis in human glioblastoma and lung cancer cells.
Mol Cell, 2021, S1097-2765(21)00729-2
Prog Neurobiol, 2021, S0301-0082(21)00137-4
Int J Mol Sci, 2021, 22(4)2046
S7888 Spautin-1 Spautin-1 is a potent and specific autophagy inhibitor, and inhibits the deubiquitinating activity of USP10 and USP13 with IC50 of ∼0.6-0.7 μM. Spautin-1 enhances apoptosis.
J Clin Invest, 2021, 146893
Protein Cell, 2021, 10.1007/s13238-021-00858-3
Autophagy, 2021, 1-19
S7948 MRT67307 HCl MRT67307 is a potent and dual IKKϵ and TBK1 inhibitor with IC50 of 160 and 19 nM, respectively. MRT67307 potently inhibits ULK1 and ULK2 and blocks autophagy.
Cell, 2021, S0092-8674(21)00885-0
Cell Rep, 2020, 33(5):108339
Cancer Discov, 2020, 10(3):382-393
S7949 MRT68921 HCl MRT68921 is a potent and dual autophagy kinase ULK1/2 inhibitor with IC50 of 2.9 nM and 1.1 nM, respectively.
Mol Cell, 2021, 81(9):2013-2030.e9
Cell Rep, 2021, 36(13):109762
Cancer Biol Med, 2021, j.issn.2095-3941.2020.0262
S8037 Necrostatin-1 Necrostatin-1 (Nec-1) is a specific RIP1 (RIPK1) inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM in 293T cells. Necrostatin-1 also blocks IDO and suppresses autophagy and apoptosis.
Cell, 2021, S0092-8674(21)00885-0
Nat Immunol, 2021, 22(9):1107-1117
Adv Sci (Weinh), 2021, 8(10):2004680
S8222 AS1842856 AS1842856 is a cell-permeable inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM. It could directly bind to the active Foxo1, but not the Ser256-phosphorylated form. AS1842856 suppresses autophagy.
J Clin Invest, 2021, 131(1)135937
Int J Mol Sci, 2021, 22(6)3028
Invest Ophthalmol Vis Sci, 2021, 62(3):37
S8274 STO-609 STO-609 is a specific inhibitor of the Ca2+/Calmodulin-dependent protein kinase kinase(CaM-KK) that inhibits the activities of recombinant CaM-KKα and CaM-KKβ isoforms, with Ki values of 80 and 15 ng/ml, respectively, and also inhibits their autophosphorylation activities. STO-609 inhibits AMPKK activity and inhibits autophagy.
Cell Res, 2021, 10.1038/s41422-021-00565-y
Autophagy, 2021, 1-14
Cell Death Dis, 2021, 12(11):972
S8317 3BDO 3BDO, a butyrolactone derivative, could target FKBP1A and activate the mTOR signaling pathway. It inhibits autophagy in HUVECs. 3BDO inhibits oxLDL-induced apoptosis.
Front Oncol, 2021, 11:665420
Mol Med Rep, 2021, 24(2)592
Biomed Res Int, 2020, 2020:4035306
S8369 Lys05 Lys05 is a new lysosomal autophagy inhibitor which potently accumulates within and deacidifies the lysosome of both cells and tumors, resulting in sustained inhibition of autophagy and tumor growth.
Blood Cancer J, 2021, 11(6):111
Surgery, 2021, S0039-6060(21)00795-9
Environ Toxicol, 2021, 10.1002/tox.23355
S8527 ROC-325 ROC-325 is an orally available novel inhibitor of lysosomal-mediated autophagy which diminishes AML cell viability with the IC50 range of 0.7-2.2 μM.
S8576 EAD1 EAD1 is a potent autophagy inhibitor with an IC50 of 5.8 μM in the BxPC3 cells. It has antiproliferative activities in lung and pancreatic cancer cells.
Autophagy, 2021, 1-17
S8596 Autophinib Autophinib is a potent autophagy inhibitor with a novel chemotype with IC50 values of 90 and 40 nM for autophagy in starvation induced autophagy assay and rapamycin induced autophagy assay. The IC50 value for Vps34 is 19 nM in vitro.
Nat Genet, 2021, 53(4):435-444
J Agric Food Chem, 2021, 69(40):11847-11855
J Steroid Biochem Mol Biol, 2021, 209:105826
S8744 PHY34 PHY34 is a late-stage autophagy inhibitor with nanomolar potency and significant antitumor efficacy as a single agent against HGSOC in vivo.
S8764 IITZ-01 IITZ-01 is a potent autophagy inhibitor, enhancing autophagosome accumulation but inhibiting autophagosomal degradation by impairing lysosomal function.
Cancers (Basel), 2020, 12(9):E2363
S8793 ULK-101 ULK-101 is a potent and selective ULK1 inhibitor with IC50 values of 8.3 nM and 30 nM for ULK1 and ULK2, respectively.
J Virol, 2021, JVI0155021
Mol Carcinog, 2021, 10.1002/mc.23357
Cell Signal, 2021, 85:110040
S8807 PFK158 PFK158 is a potent and selective inhibitor of PFKFB3. It has improved PK properties and causes ~80% growth inhibition in several mouse models of human-derived tumors.
Front Immunol, 2021, 12:669456
Cancer Metab, 2021, 9(1):33
Cell Metab, 2020, 5;31(5):937-955e7
S8808 DC661 DC661 is capable of deacidifying the lysosome and inhibiting autophagy significantly better than hydroxychloroquine (HCQ). DC661 induces apoptosis.
Biomed Pharmacother, 2022, 145:112432
Nature, 2021, 10.1038/s41586-021-04204-9
Cell Death Dis, 2021, 12(3):239
S9150 Daurisoline Daurisoline, a bis-benzylisoquinoline alkaloid isolated from the rhizomes of Menispermum dauricum, is a potent autophagy blockers with antiarrhythmic effects.
S9424 Liensinine diperchlorate Liensinine, a major isoquinoline alkaloid, inhibits late-stage autophagy/mitophagy through blocking autophagosome-lysosome fusion. It is a novel autophagy/mitophagy inhibitor.
A5123 ATG9A Rabbit Recombinant mAb ATG9A Rabbit Recombinant mAb detects endogenous level of total ATG9A.
A5151 Atg4B Rabbit Recombinant mAb Atg4B Rabbit Recombinant mAb detects endogenous level of Atg4B.
S0012 E260 E260 (Fer and FerT inhibitor E260) is a Fer kinase and FerT inhibitor that selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level.
S0709 Tubastatin A TFA Tubastatin A TFA (Tubastatin A trifluoroacetate salt) is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
S1002 ABT-737 ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in cell-free assays, respectively; no inhibition observed against Mcl-1, Bcl-B or Bfl-1. ABT-737 induces mitochondrial pathway apoptosis and mitophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
Cell Death Dis, 2021, 12(8):736
Cell Death Dis, 2021, 12(11):1011
S1003 Linifanib (ABT-869) Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.
Cancer Lett, 2021, 507:80-88
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
S1004 Veliparib (ABT-888) Veliparib (ABT-888, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increases autophagy and apoptosis. Phase 3.
Cell, 2022, 185(1):169-183.e19
Transl Oncol, 2022, 15(1):101283
Sci Transl Med, 2021, 13(592)eabc7211
S1006 Saracatinib (AZD0530) Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM in cell-free assays, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). Saracatinib induces autophagy. Phase 2/3.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Nat Commun, 2021, 12(1):6941
S1009 Dactolisib (BEZ235) Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
Nat Commun, 2021, 12(1):7268
EMBO Mol Med, 2021, e14511
Cell Rep, 2021, 34(11):108870
S1011 Afatinib (BIBW2992) Afatinib (BIBW2992) inhibits EGFR/ErbB irreversibly in vitro with IC50 of 0.5, 0.4, 10, 14, 1 nM for EGFRwt, EGFR L858R , EGFR L858R/T790M ErbB2 (HER2) and ErbB4 (HER4), respectively. Afatinib induces autophagy.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(20)30609-7
Nat Cell Biol, 2021, 23(4):377-390
S1014 Bosutinib (SKI-606) Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.
Nat Commun, 2021, 12(1):6941
Cancer Res, 2021, 81(21):5438-5450
Cancer Res, 2021, canres.0613.2021
S1017 Cediranib (AZD2171) Cediranib (AZD2171, NSC-732208) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3 in HUVEC cells. Cediranib (AZD2171) induces autophagic vacuole accumulation. Phase 3.
Hum Mol Genet, 2021, ddab009
Sci Rep, 2021, 11(1):9362
Sci Rep, 2021, 11(1):23302
S1021 Dasatinib (BMS-354825) Dasatinib (BMS-354825) is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. Dasatinib induces autophagy and apoptosis with anti-tumor activity.
Nat Immunol, 2021, 10.1038/s41590-021-00948-8
Acta Neuropathol, 2021, 10.1007/s00401-021-02327-x
Nat Commun, 2021, 12(1):3705
S1023 Erlotinib HCl (OSI-744) Erlotinib HCl (OSI-744, CP358774, NSC 718781) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.
Nat Cell Biol, 2021, 23(4):377-390
Sci Adv, 2021, 7(10)eabe8671
Nat Commun, 2021, 12(1):4789
S1025 Gefitinib (ZD1839) Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.
Nature, 2021, 595(7869):730-734
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Cell Biol, 2021, 23(4):377-390
S1026 Imatinib (STI571) Mesylate Imatinib (STI571, CGP057148B, Gleevec) Mesylate is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. Imatinib Mesylate (STI571) induces autophagy.
Cancer Cell, 2021, S1535-6108(21)00659-0
Clin Cancer Res, 2021, 27(9):2533-2548
Cell Rep, 2021, 37(1):109788
S1027 FL-411 FL-411 (BRD4-IN-1) is a potent and selective inhibitor of Bromodomain-containing protein 4 (BRD4) with IC50 of 0.43 μM for BRD4(1). FL-411 induces ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction.
S1030 Panobinostat (LBH589) Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.
Nat Med, 2021, 10.1038/s41591-020-01212-6
Cell Stem Cell, 2021, 28(1):48-62.e6
Hepatology, 2021, 10.1002/hep.32245
S1033 Nilotinib (AMN-107) Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
Cancer Cell, 2021, S1535-6108(21)00659-0
EMBO Mol Med, 2021, e11814
Cancer Res, 2021, canres.1222.2021
S1035 Pazopanib HCl (GW786034 HCl) Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces autophagic Type II cell death.
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancers (Basel), 2021, 13(14)3635
J Clin Endocrinol Metab, 2021, dgab020
S1038 PI-103 PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. PI-103 induces apoptosis in murine T-cell Lymphoma.
Adv Healthc Mater, 2021, e2101944
Cell Chem Biol, 2021, S2451-9456(21)00254-3
Neurobiol Dis, 2021, 156:105407
S1039 Rapamycin (AY-22989) Rapamycin (AY-22989, Rapamune, Sirolimus, NSC-2260804) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
J Cell Biol, 2022, 221(1)e202103033
Bone, 2022, 154:116262
Neural Regen Res, 2022, 17(4):824-831
S1040 Sorafenib (BAY 43-9006) tosylate Sorafenib (BAY 43-9006) tosylate is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
Cancer Cell, 2021, S1535-6108(21)00659-0
Leukemia, 2021, 10.1038/s41375-021-01308-z
Theranostics, 2021, 11(12):5650-5674
S1044 Temsirolimus (CCI-779) Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis.
Mol Syst Biol, 2021, 17(8):e10239
Cell Death Dis, 2021, 12(1):108
J Clin Endocrinol Metab, 2021, dgab020
S1046 Vandetanib (ZD6474) Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).
J Clin Endocrinol Metab, 2021, dgab020
Cell Chem Biol, 2021, S2451-9456(21)00303-2
Cancer Discov, 2021, candisc.1201.2020
S1047 Vorinostat (SAHA) Vorinostat (suberoylanilide hydroxamic acid, SAHA, MK0683, Zolinza) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
Adv Sci (Weinh), 2021, e2103360
Hepatology, 2021, 10.1002/hep.32245
Nat Commun, 2021, 12(1):4404
S1048 Tozasertib (VX-680, MK-0457) Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.
Science, 2021, 371(6535)eabc5386
J Cell Biol, 2021, 220(2)e202008029
EMBO Rep, 2021, e51503
S1049 Y-27632 2HCl Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM in a cell-free assay, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK.
Nature, 2021, 600(7888):285-289
Nature, 2021, 593(7859):440-444
Cell, 2021, 184(25):6119-6137.e26
S1053 Entinostat (MS-275) Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Science, 2021, 372(6537)eaba1786
Nat Chem Biol, 2021, 10.1038/s41589-021-00772-z
Nat Commun, 2021, 12(1):2699
S1057 Obatoclax Mesylate (GX15-070) Obatoclax Mesylate (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 3.
Cancer Res, 2021, canres.0955.2021
Transl Oncol, 2021, 14(8):101116
Biomaterials, 2020, 232:119709
S1060 Olaparib (AZD2281) Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutations.
Cell, 2022, 185(1):169-183.e19
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
S1065 Pictilisib (GDC-0941) Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Immunity, 2021, 54(8):1807-1824.e14
S1068 Crizotinib (PF-02341066) Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Nature, 2021, 600(7888):319-323
Cell, 2021, 184(10):2649-2664.e18
Nat Commun, 2021, 12(1):6813
S1069 Luminespib (NVP-AUY922) Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.
Cell Rep, 2021, 34(11):108870
Haematologica, 2021, 10.3324/haematol.2021.278743
Cancers (Basel), 2021, 13(15)3850
S1075 SB216763 SB216763 is a potent and selective GSK-3 inhibitor with IC50 of 34.3 nM for GSK-3α and equally effective at inhibiting human GSK-3β. SB216763 activates autophagy.
Biomed Pharmacother, 2022, 145:112432
J Clin Invest, 2021, 131(6)136098
Autophagy, 2021, 1-19
S1077 SB202190 (FHPI) SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM in cell-free assays, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo. SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. SB202190 significantly suppresses Erastin‐dependent ferroptosis.
Nature, 2021, 600(7888):314-318
Immunity, 2021, S1074-7613(21)00210-7
Nat Commun, 2021, 12(1):6941
S1078 MK-2206 2HCl MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. MK-2206 2HCl induces autophagy and apoptosis in cancer cells. Phase 2.
Cancer Cell, 2021, S1535-6108(21)00383-4
Immunity, 2021, S1074-7613(21)00069-8
Cell Res, 2021, 10.1038/s41422-021-00528-3
S1080 SU11274 SU11274 (PKI-SU11274) is a selective Met (c-Met) inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. SU11274 induces autophagy, apoptosis and cell cycle arrest.
Cell Rep, 2021, 37(5):109905
Signal Transduct Target Ther, 2021, 6(1):401
Cell Chem Biol, 2021, S2451-9456(21)00303-2
S1085 Belinostat (PXD101) Belinostat (PXD101, NSC726630, PX-105684) is a novel HDAC inhibitor with IC50 of 27 nM in a cell-free assay, with activity demonstrated in cisplatin-resistant tumors. Belinostat (PXD101) induces autophagy.
Adv Sci (Weinh), 2021, e2103360
Hepatology, 2021, 10.1002/hep.32245
Nat Commun, 2021, 12(1):117
S1107 Danusertib (PHA-739358) Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2.
Cancers (Basel), 2021, 13(6)1205
Life Sci Alliance, 2021, 4(8)e202101019
Mol Cell, 2020, 80(6):1104-1122.e9
S1120 Everolimus (RAD001) Everolimus (RAD001, SDZ-RAD) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay. Everolimus induces cell apoptosis and autophagy and inhibits tumor cells proliferation.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Gut, 2021, gutjnl-2020-322660
S1122 Mocetinostat (MGCD0103) Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.
Cancer Cell, 2021, S1535-6108(20)30662-0
Nat Commun, 2021, 12(1):5056
Cancers (Basel), 2021, 13(15)3862
S1129 SRT1720 HCl SRT1720 HCl is a selective SIRT1 activator with EC50 of 0.16 μM in a cell-free assay, but is >230-fold less potent for SIRT2 and SIRT3. SRT1720 induces autophagy.
Neuro Oncol, 2021, 23(1):53-62
Theranostics, 2021, 11(2):893-905
Oncogene, 2021, 10.1038/s41388-021-01999-9
S1130 YM155 (Sepantronium Bromide) YM155 (Sepantronium Bromide) is a potent survivin suppressant by inhibiting Survivin promoter activity with IC50 of 0.54 nM in HeLa-SURP-luc and CHO-SV40-luc cells; does not significantly inhibit SV40 promoter activity, but is observed to slightly inhibit the interaction of Survivin with XIAP. YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells. Phase 2.
Nat Commun, 2021, 12(1):2877
Nat Commun, 2021, 12(1):2475
J Clin Invest, 2021, 131(10)146777
S1133 Alisertib (MLN8237) Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.
Cancer Cell, 2021, S1535-6108(21)00383-4
Cancer Cell, 2021, S1535-6108(21)00492-X
Cancer Cell, 2021, S1535-6108(21)00338-X
S1135 Pemetrexed (LY-231514) disodium Pemetrexed (LY-231514) disodium is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.
J Exp Clin Cancer Res, 2021, 40(1):344
Br J Cancer, 2021, 10.1038/s41416-021-01441-7
Cell Chem Biol, 2021, S2451-9456(21)00442-6
S1141 Tanespimycin (17-AAG) Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.
Cell Stem Cell, 2021, S1934-5909(21)00294-0
Mol Cell, 2021, 81(6):1170-1186.e10
EMBO Rep, 2021, e51740
S1149 Gemcitabine (LY-188011) HCl Gemcitabine (LY-188011, NSC 613327) HCl is a DNA synthesis inhibitor with IC50 of 50 nM, 40 nM, 18 nM and 12 nM in PANC1, MIAPaCa2, BxPC3 and Capan2 cells, respectively.
Cell, 2021, 184(25):6119-6137.e26
Nat Commun, 2021, 12(1):4917
Nat Commun, 2021, 12(1):1602
S1166 Cisplatin (NSC 119875) Cisplatin (NSC 119875, Cisplatinum, cis-diamminedichloroplatinum II, CDDP, cis DDP, DDP) is an inorganic platinum complex, which is able to inhibit DNA synthesis by conforming DNA adducts in tumor cells. Cisplatin activates ferroptosis and induces autophagy. Solutions are best fresh-prepared.
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Commun, 2021, 12(1):5404
Nat Commun, 2021, 12(1):7064
S1168 Valproic Acid (NSC 93819) sodium salt Valproic Acid sodium salt (NSC 93819, Sodium valproate) is a HDAC inhibitor by selectively inducing proteasomal degradation of HDAC2, used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. Valproic acid induces Notch1 signaling in small cell lung cancer (SCLC) cells. Valproic acid is under investigation for treatment of HIV and various cancers. Valproic acid (VPA) induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α.
Pigment Cell Melanoma Res, 2021, 10.1111/pcmr.13014
Front Immunol, 2021, 12:771453
Front Oncol, 2021, 11:723966
S1178 Regorafenib (BAY 73-4506) Regorafenib (BAY 73-4506, Fluoro-Sorafenib, Resihance, Stivarga) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy.
Cancer Cell, 2021, S1535-6108(21)00659-0
Adv Sci (Weinh), 2021, e2103360
ACS Appl Mater Interfaces, 2021, 13(41):48478-48491
S1190 Bicalutamide (ICI-176334) Bicalutamide (ICI-176334) is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. Bicalutamide promotes autophagy.
Sci Adv, 2021, 7(27)eabg2564
Cell Rep, 2021, 36(10):109625
Cancer Lett, 2021, 520:172-183
S1191 Fulvestrant (ICI-182780) Fulvestrant (ICI-182780, ZD 9238, ZM 182780) is an estrogen receptor (ER) antagonist with IC50 of 0.94 nM in a cell-free assay. Fulvestrant also induces autophagy and apoptosis and has antitumor activity.
Biochim Biophys Acta Gen Subj, 2022, 1866(1):130046
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-2961
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
S1218 Clofarabine Clofarabine (Clolar) inhibits the enzymatic activities of ribonucleotide reductase (RNR) (IC50 = 65 nM) and DNA polymerase. Clofarabine induces autophagy and apoptosis.
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
iScience, 2021, 24(9):103080
S1219 YM201636 YM201636 is a selective PIKfyve inhibitor with IC50 of 33 nM, less potent to p110α and insensitive to Fabl (yeast orthologue). YM-201636 suppresses the growth of liver cancer via the induction of autophagy.
Cell Rep, 2021, 35(1):108940
Front Oncol, 2021, 11:620873
J Biol Methods, 2021, 8(1):e143
S1224 Oxaliplatin (NSC 266046) Oxaliplatin (NSC 266046, L-OHP, Eloxatin) is a DNA alkylating agent that activates autophagy. Oxaliplatin inhibits DNA synthesis by conforming DNA adducts in RT4, TCCSUP, A2780, HT-29, U-373MG, U-87MG, SK-MEL-2, and HT-144 cells. DMF is recommended for dissolution. Solutions are best fresh-prepared.
Cell, 2021, 184(25):6119-6137.e26
Cancer Cell, 2021, S1535-6108(21)00659-0
Adv Sci (Weinh), 2021, e2103360
S1225 Etoposide (VP-16) Etoposide (VP-16, VP-16213) is a semisynthetic derivative of podophyllotoxin, which inhibits DNA synthesis via topoisomerase II inhibition activity. Etoposide induces autophagy, mitophagy and apoptosis.
Nature, 2021, 10.1038/s41586-021-04204-9
Nature, 2021, 10.1038/s41586-021-04009-w
Cancer Cell, 2021, S1535-6108(21)00659-0
S1228 Idarubicin HCl Idarubicin HCl (4-demethoxydaunorubicin, NSC256439, 4-DMDR) is a hydrochloride salt form of Idarubicin which is an anthracycline antibiotic and a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells with IC50 of 3.3 ng/mL in a cell-free assay. Idarubicin induces mTOR-dependent cytotoxic autophagy.
Cancers (Basel), 2021, 13(14)3586
Biomolecules, 2021, 11(8)1128
Int J Mol Sci, 2021, 22(3)1362
S1230 Flavopiridol (L86-8275) Flavopiridol (L86-8275, Alvocidib, NSC 649890, HMR-1275) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol induces autophagy and ER stress. Flavopiridol blocks HIV-1 replication. Phase 1/2.
Nature, 2021, 10.1038/s41586-021-03445-y
Genome Res, 2021, 31(6):981-994
J Cell Biol, 2021, 220(7)e202008146
S1231 Topotecan (NSC609699) HCl Topotecan HCl (NSC609699, Nogitecan, SKFS 104864A) is a topoisomerase I inhibitor for MCF-7 Luc cells and DU-145 Luc cells with IC50 of 13 nM and 2 nM in cell-free assays, respectively. Topotecan HCl induces autophagy and apoptosis.
Cancer Cell, 2021, S1535-6108(21)00659-0
Cancer Res, 2021, canres.1540.2020
Cell Rep, 2021, 34(10):108814
S1233 2-Methoxyestradiol (2-MeOE2) 2-Methoxyestradiol (2-MeOE2, NSC 659853, 2-ME2) depolymerizes microtubules and blocks HIF-1α nuclear accumulation and HIF-transcriptional activity. 2-Methoxyestradiol induces both autophagy and apoptosis in various carcinogenic cell lines. Phase 2.
Cell Death Differ, 2021, 10.1038/s41418-021-00885-x
Cancers (Basel), 2021, 13(20)5232
Cell Death Discov, 2021, 7(1):242
S1235 Letrozole (CGS 20267) Letrozole (CGS 20267) is a third generation inhibitor of aromatase with IC50 of 0.07-20 nM in cell-free assays.It has no effect on the plasma levels of 17α-OH progesterone, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), or androstenedione and does not affect normal urine electrolyte excretion or thyroid function in clinical studies. Letrozole induces autophagy.
Mol Hum Reprod, 2021, 27(4)gaab013
Steroids, 2021, 177:108935
Hum Cell, 2021, 10.1007/s13577-021-00639-4
S1237 Temozolomide (CCRG 81045) Temozolomide (CCRG81045, NSC 362856, TMZ) is a monofunctional SN-1 alkylating agent that can modify nitrogen atoms in the DNA ring and the extracyclic oxygen group, chemically converted to MTIC and degrades to methyldiazonium cation, which transfers methyl groups to DNA at physiologic pH. A DNA damage inducer in L-1210 and L-1210/BCNU cells. Temozolomide induces apoptosis and exhibits antitumor activity.
Cell Res, 2021, 10.1038/s41422-021-00528-3
Clin Cancer Res, 2021, clincanres.2092.2021
Theranostics, 2021, 11(4):1991-2005
S1238 Tamoxifen (ICI 46474) Tamoxifen (ICI 46474, (Z)-Tamoxifen, trans-Tamoxifen) is a selective estrogen receptor modulator (SERM). Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis.
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
Cancers (Basel), 2021, 13(9)2116
Cell Death Dis, 2021, 12(6):619
S1250 Enzalutamide (MDV3100) Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is shown to increase autophagy.
Nat Med, 2021, 27(3):426-433
Nat Med, 2021, 10.1038/s41591-020-01168-7
J Extracell Vesicles, 2021, 10(10):e12136
S1263 CHIR-99021 (CT99021) CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. CHIR99021 functions as a Wnt/β-catenin activator and induces autophagy.
Cell, 2021, 184(11):2843-2859.e20
Nat Genet, 2021, 53(12):1686-1697
Nat Genet, 2021, 53(4):467-476
S1267 Vemurafenib (PLX4032) Vemurafenib (PLX4032, RG7204, RO5185426) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00837-3
Cancer Cell, 2021, S1535-6108(21)00659-0
Cell Metab, 2021, S1550-4131(21)00180-7
S1290 Celastrol (NSC 70931) Celastrol (NSC 70931, Tripterine) is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy.
Mol Oncol, 2021, 10.1002/1878-0261.12936
Aging (Albany NY), 2021, 13(12):16816-16833
Molecules, 2021, 26(14)4124
S1312 Streptozotocin (STZ) Streptozotocin (STZ, NSC-85998, Streptozocin, U 9889) is a glucosamine-nitrosourea derivative, which is a DNA-methylating, carcinogenic, antibiotic and diabetes inducing agent. Streptozotocin induces autophagy and apoptosis. Solutions are best fresh-prepared.
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Epigenomics, 2020, 12(20):1811-1824
S1314 Zoledronic acid (ZOL 446) Zoledronic acid (ZOL 446, ZA, Zoledronate, CGP-4244, GP42446A, Zometa, Zomera, Aclasta, Reclast), a potent osteoclast inhibitor, induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho. Zoledronic acid (ZA) also induces autophagy.
Biomater Sci, 2021, 10.1039/d0bm02107e
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Hum Cell, 2021, 10.1007/s13577-021-00639-4
S1322 Dexamethasone (MK-125) Dexamethasone (MK-125, NSC 34521, Hexadecadrol, Prednisolone F) is a potent synthetic member of the glucocorticoid class of steroid drugs, and an interleukin receptor modulator that has anti-inflammatory and immunosuppressant effects. Dexamethasone induces autophagy and mitophagy. Dexamethasone is tested in hospitalized patients with COVID-19 and is found to have benefits for critically ill patients.
Mol Syst Biol, 2021, 17(9):e10426
Cell Rep, 2021, 36(2):109360
Cell Rep, 2021, 37(5):109912
S1351 Ivermectin (MK-933) Ivermectin (MK-933, IVM) is a glutamate-gated chloride channel (GluCls) activator, used as a broad-spectrum antiparasitic drug. Ivermectin (MK-933, IVM) is a specific positive allosteric effector of P2X4 and α7 nicotinic acetylcholine receptors (nAChRs). Ivermectin has potent antiviral activity towards both HIV-1 and dengue virus. Ivermectin induces autophagy through the AKT/mTOR signaling pathway and mitophagy.
J Virol, 2021, JVI0148121
BMC Cancer, 2021, 21(1):1307
Nat Cell Biol, 2020,
S1378 Ruxolitinib (INCB018424) Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Cancer Cell, 2021, S1535-6108(21)00492-X
Sci Immunol, 2021, 6(59)eabi9007
Sci Adv, 2021, 7(50):eabl5182
S1389 Omeprazole Omeprazole is a proton pump inhibitor that blocks H(+)-K(+)-ATPase, used to treat dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, laryngopharyngeal reflux, and Zollinger–Ellison syndrome.
Theranostics, 2021, 11(5):2364-2380
J Virol, 2021, JVI.00190-21
Biosci Rep, 2021, BSR20200842
S1396 Resveratrol (SRT501) Resveratrol (SRT501, trans-Resveratrol) has a wide spectrum of targets including cyclooxygenases(i.e. COX, IC50=1.1 μM), lipooxygenases(LOX, IC50=2.7 μM), kinases, sirtuins and other proteins. It has anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects. Resveratrol induces mitophagy/autophagy and autophagy-dependent apoptosis.
Adv Sci (Weinh), 2021, e2103360
Front Immunol, 2021, 12:685523
Int J Mol Sci, 2021, 22(5)2354
S1403 Tigecycline (GAR-936) Tigecycline (GAR-936) is bacteriostatic and is a protein synthesis inhibitor by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation. Tigecycline induces autophagy by downregulating the PI3K-AKT-mTOR pathway.
iScience, 2021, 24(11):103350
Biomolecules, 2020, 10(10)E1395
Aging (Albany NY), 2020, 12(12):11364-11385
S1555 AZD8055 AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.
Nature, 2021, 591(7849):288-292
Immunity, 2021, S1074-7613(21)00069-8
Sci Adv, 2021, 7(40):eabj2485
S1573 Fasudil (HA-1077) HCl Fasudil (HA-1077, AT-877), a potent and selective inhibitor of Rho kinase, displays less potent inhibiton over PKA, PKG, PKC and MLCK with Ki of 1.6, 1.6, 3.3, and 36 μM in cell-free assays, respectively. Fasudil is also a calcium channel blocker.
Proc Natl Acad Sci U S A, 2021, 118(2)e2016034118
J Neurochem, 2021, 10.1111/jnc.15436
Front Microbiol, 2021, 12:775083
S1576 Sulfasalazine (NSC 667219) Sulfasalazine (NSC 667219, Azulfidine, Salazopyrin, Sulphasalazine) is a sulfa derivative of mesalazine, used as an anti-inflammatory agent to treat bowel disease and rheumatoid arthritis. Sulfasalazine is a potent and specific inhibitor of nuclear factor kappa B (NF-κB), TGF-β and COX-2. Sulfasalazine induces ferroptosis, apoptosis and autophagy.
Cell Metab, 2021, S1550-4131(21)00233-3
Sci Adv, 2021, 7(35)eabj0364
Sci Adv, 2021, 7(27)eabh3032
S1582 H 89 2HCl H 89 2HCl is a potent PKA inhibitor with Ki of 48 nM in a cell-free assay, 10-fold selective for PKA than PKG,500-fold greater selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II. H 89 2HCl induces autophagy.
Sci Immunol, 2021, 6(61)eabg9698
Theranostics, 2021, 11(10):4975-4991
Cell Rep, 2021, 37(12):110137
S1590 TWS119 TWS119 is a GSK-3β inhibitor with IC50 of 30 nM in a cell-free assay; capable of inducing neuronal differentiation and may be useful to stem cell biology. GSK-3β inhibition triggers autophagy.
Nat Commun, 2021, 12(1):4536
EMBO Rep, 2021, e51503
Cell Rep, 2021, 36(1):109311
S1648 Cytarabine (U-19920A) Cytarabine (U-19920A, Cytarabin, Ara-C, Arabinofuranosyl Cytidine, Cytosine β-D-arabinofuranoside, Cytosine arabinoside, NSC 63878, NSC 287459) is an antimetabolic agent and DNA synthesis inhibitor with IC50 of 16 nM in wild-type CCRF-CEM cells. Cytarabine induces autophagy and apoptosis.
Leukemia, 2021, 10.1038/s41375-021-01361-8
Blood Cancer J, 2021, 11(6):111
Cell Rep, 2021, 36(7):109559
S1693 Carbamazepine Carbamazepine (Carbatrol, NSC 169864) is a sodium channel blocker with IC50 of 131 μM in rat brain synaptosomes.
Front Pharmacol, 2021, 12:749930
Anticancer Res, 2021, 41(2):687-697
PLoS One, 2019, 14(2):e0211644
S1714 Gemcitabine (LY-188011) Gemcitabine (LY-188011, NSC 613327), a nucleic acid synthesis inhibitor, is a very potent and specific deoxycytidine analogue, used as chemotherapy. Gemcitabine induces a potent p53-dependent apoptosis.
Nat Commun, 2021, 12(1):1602
Cancer Res, 2021, canres.1337.2021
Cell Rep, 2021, 34(10):108814
S1747 Nimodipine Nimodipine (BAY E 9736) is a dihydropyridine calcium channel blocker and an autophagy inhibitor, used in the treatment of high blood pressure.
Cell Discov, 2020, 6(1):96
G3 (Bethesda), 2020, 4;10(5):1585-1597
Antiviral Res, 2016, 132:38-45
S1759 Pitavastatin (NK-104) calcium Pitavastatin Calcium (NK-104, P-872441, itavastatin, nisvastatin), a novel member of the medication class of statins, is a calcium salt formulation of pitavastatin which is a highly effective HMG-CoA reductase inhibitor. Pitavastatin Calcium attenuates AGEs-induced mitophagy via inhibition of ROS generation. Pitavastatin Calcium induces autophagy and apoptosis.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Cancer Discov, 2021, candisc.0551.2021
Transl Oncol, 2021, 14(7):101107
S1782 Azacitidine (5-Azacytidine) Azacitidine (5-Azacytidine, 5-AzaC, Ladakamycin, AZA, 5-Aza, CC-486) is a nucleoside analogue of cytidine that specifically inhibits DNA methylation by trapping DNA methyltransferases. Azacitidine induces mitochondrial apoptosis and autophagy.
Clin Cancer Res, 2021, clincanres.2486.2019
Int J Cancer, 2021, 10.1002/ijc.33865
J Hematol Oncol, 2021, 14(1):70
S1792 Simvastatin (MK 733) Simvastatin (MK-0733, MK 733) is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Theranostics, 2021, 11(4):1609-1625
Theranostics, 2021, 11(13):6560-6572
S1794 Fenofibrate (NSC-281319) Fenofibrate (NSC-281319) is a compound of the fibrate class and fibric acid derivative. Fenofibrate is a selective agonist of PPARα with EC50 of 30 μM. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with IC50 of 0.2 μM, 0.7 μM and 9.7 μM for CYP2C19, CYP2B6 and CYP2C9, respectively. Fenofibrate induces autophagy.
Redox Biol, 2021, 46:102082
J Cell Mol Med, 2020, 24(6):3384-3398
J Cell Mol Med, 2020, 24(6):3384-3398
S1837 Flubendazole Flubendazole (Flumoxanal, NSC 313680) is an autophagy inducer by targeting Atg4B, used to treat internal parasite and worm infection.
Sci Rep, 2020, 10(1):13124
RSC Advances, 2018, 10.1039/C7RA12259D
S1847 Clemastine (HS-592) fumarate Clemastine Fumarate (HS-592, Meclastine) is a selective histamine H1 receptor antagonist with IC50 of 3 nM. Clemastine stimulates autophagy via mTOR pathway.
Neuron, 2021, S0896-6273(21)00352-4
Neurosci Bull, 2021, 10.1007/s12264-021-00745-1
Neurochem Res, 2021, 10.1007/s11064-021-03465-0
S1848 Curcumin Curcumin (Diferuloylmethane, Natural Yellow 3, Turmeric yellow) is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family (Zingiberaceae). It is an inhibitor of p300 histone acetylatransferase(IC50~25 μM)and Histone deacetylase (HDAC); activates Nrf2 pathway and supresses the activation of NF-κB. Curcumin induces mitophagy, autophagy, apoptosis, and cell cycle arrest with antitumor activity. Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis-mediated cell death. Curcumin exhibits anti-infective properties against various human pathogens like the influenza virus, hepatitis C virus, HIV and so on.
Adv Sci (Weinh), 2021, e2103360
Front Immunol, 2021, 12:656242
Aging (Albany NY), 2021, 13(10):13968-14000
S1896 Hydroxyurea (NSC-32065) Hydroxyurea (NSC-32065, NCI-C04831, Hydroxycarbamide) is an antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxyurea activates apoptosis and autophagy. Hydroxyurea is used to treat HIV infection.
Nat Commun, 2021, 12(1):5572
Cancer Res, 2021, canres.3761.2020
Cell Death Dis, 2021, 12(2):183
S1950 Metformin HCl Metformin HCl (1,1-Dimethylbiguanide HCl) decreases hyperglycemia in hepatocytes primarily by suppressing glucose production by the liver (hepatic gluconeogenesis). Metformin promotes mitophagy in mononuclear cells. Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153.
Immunity, 2021, S1074-7613(21)00210-7
Cell Res, 2021, 10.1038/s41422-021-00565-y
Mol Cell, 2021, S1097-2765(21)00232-X
S1972 Tamoxifen (ICI 46474) Citrate Tamoxifen Citrate (ICI 46474) is a selective estrogen receptor modulator (SERM). Tamoxifen Citrate is also a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis and autophagy.
Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3905
Cancers (Basel), 2021, 13(9)2116
Cell Death Dis, 2021, 12(6):619
S1979 Amiodarone (NSC 85442) HCl Amiodarone (NSC 85442) HCl is a sodium/potassium-ATPase inhibitor and an autophagy activator, used to treat various types of cardiac dysrhythmias.
Front Cell Infect Microbiol, 2021, 11:630812
Drug Metab Dispos, 2020, 48(8):613-621
Cell Syst, 2019, 8(2):97-108
S1999 Sodium butyrate Sodium butyrate (NaB, Butanoic acid sodium salt), sodium salt of butyric acid, is a histone deacetylase inhibitor and competitively binds to the zinc sites of class I and II histone deacetylases (HDACs). Sodium butyrate (NaB) inhibits cell cycle progression, promotes differentiation, and induces apoptosis and autophagy in several types of cancer cells.
Cell Mol Life Sci, 2021, 10.1007/s00018-021-03883-x
Front Cell Dev Biol, 2021, 9:662868
Int J Mol Sci, 2020, 21(2)
S2061 Lovastatin (MK-803) Lovastatin (MK-803, Mevinolin) is an inhibitor of HMG-CoA reductase with IC50 of 3.4 nM in a cell-free assay, used for lowering cholesterol (hypolipidemic agent). Lovastatin triggers autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Sci Adv, 2021, 7(29)eabg3188
Cancer Res, 2021, canres.0955.2021
S2077 Atorvastatin Calcium Atorvastatin Calcium is an inhibitor of HMG-CoA reductase used as a cholesterol-lowering medication that blocks the production of cholesterol. Atorvastatin Calcium induces apoptosis and autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Oncol Lett, 2021, 21(2):82
Neurobiol Dis, 2021, 152:105294
S2111 Lapatinib (GW-572016) Lapatinib (GW-572016, GSK572016, GW2016), used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death.
Cancer Cell, 2021, S1535-6108(21)00659-0
Nat Cell Biol, 2021, 23(4):377-390
Gut, 2021, 70(5):890-899
S2163 PF-4708671 PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. PF-4708671 induces autophagy. First S6K1-specific inhibitor to be reported.
Mol Cell, 2021, S1097-2765(21)00497-4
Cancers (Basel), 2021, 13(8)1909
Cell Death Dis, 2021, 12(1):108
S2180 Ixazomib (MLN2238) Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Ixazomib (MLN2238) induces autophagy. Phase 3.
Pharmaceutics, 2021, 13(3)314
Biomedicines, 2021, 9(1)E33
Cell, 2020, 182(3):685-712.e19
S2181 Ixazomib Citrate (MLN9708) Analogue Ixazomib Citrate (MLN9708) Analogue is the analogue of Ixazomib Citrate (MLN9708) from WO2016165677A1. Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/Ki of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.
Autophagy, 2021, 1-19
Cell Chem Biol, 2021, S2451-9456(21)00400-1
S2198 SGI-1776 free base SGI-1776 free base is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM in a cell-free assay, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin. SGI-1776 induces apoptosis and autophagy. Phase 1.
Cancer Res, 2021, canres.1023.2021
Commun Biol, 2021, 4(1):1221
Cell, 2020, 182(3):685-712.e19
S2218 Torkinib (PP242) Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and apoptosis.
Immunity, 2021, 54(10):2354-2371.e8
Sci Adv, 2021, 7(46):eabi6439
Mol Cancer, 2021, 20(1):85
S2219 Momelotinib (CYT387) Momelotinib (CYT387, LM-1149 , CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.
Cell Stem Cell, 2021, S1934-5909(21)00344-1
Cancer Res, 2021, canres.0955.2021
J Transl Med, 2021, 19(1):396
S2226 Idelalisib (CAL-101, GS-1101) Idelalisib (CAL-101, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Mol Cell, 2021, 81(4):708-723.e5
J Exp Med, 2021, 218(12)e20211035
J Exp Med, 2021, 218(2)e20200517
S2248 Silmitasertib (CX-4945) Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, less potent to Flt3, Pim1 and CDK1 (inactive in cell-based assay). Silmitasertib induces autophagy and promotes apoptosis. Phase 1/2.
Genes Dev, 2021, 35(15-16):1123-1141
Elife, 2021, 10e65962
J Med Chem, 2021, 10.1021/acs.jmedchem.1c00063
S2285 Cryptotanshinone Cryptotanshinone is a STAT3 inhibitor with IC50 of 4.6 μM in a cell-free assay, strongly inhibits phosphorylation of STAT3 Tyr705, with a small effect on STAT3 Ser727, but none against STAT1 nor STAT5. Cryptotanshinone induces ROS-dependent autophagy and mitochondria-mediated apoptosis.
Front Immunol, 2021, 12:712781
Int J Biol Sci, 2021, 17(10):2417-2429
J Cell Mol Med, 2021, 10.1111/jcmm.16250
S2290 Dihydroartemisinin (DHA) Dihydroartemisinin (DHA, Dihydroqinghaosu, β-Dihydroartemisinin, Artenimol) is a semi-synthetic derivative of artemisinin and isolated from the traditional Chinese herb Artemisia annua. Dihydroartemisinin induces autophagy and apoptosis by suppressing NF-κB activation.
Nat Immunol, 2021, 10.1038/s41590-021-00967-5
ACS Infect Dis, 2021, 10.1021/acsinfecdis.0c00580
Mol Med Rep, 2021, 23(1)40
S2310 Honokiol (NSC 293100) Honokiol (NSC 293100) is the active principle of magnolia extract that inhibits Akt-phosphorylation and promotes ERK1/2 phosphorylation. Honokiol causes G0/G1 phase arrest, induces apoptosis, and autophagy via the ROS/ERK1/2 signaling pathway. Honokiol inhibits hepatitis C virus (HCV) infection. Phase 3.
Cell Death Dis, 2021, 12(9):847
Front Cell Dev Biol, 2021, 9:619475
Am J Cancer Res, 2021, 11(6):3039-3054
S2391 Quercetin (NSC 9221) Quercetin (NSC 9221, Sophoretin, C.I. 75720), a natural flavonoid present in vegetables, fruit and wine, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4-5.4 μM. Quercetin induces mitophagy, apoptosis and protective autophagy. Phase 4.
Nucleic Acids Res, 2021, gkab538
Redox Biol, 2021, 44:102010
Front Immunol, 2021, 12:685523
S2449 Colforsin (Forskolin, HL 362) Colforsin (Forskolin, HL 362, Coleonol, Colforsin) is a ubiquitous activator of eukaryotic adenylyl cyclase (AC) in a wide variety of cell types, commonly used to raise levels of cAMP in the study and research of cell physiology. Forskolin also activates PXR and FXR activity. Forskolin stimulates autophagy.
Adv Sci (Weinh), 2021, e2100190
Sci Adv, 2021, 7(33)eabf4416
Eur Respir J, 2021, 2100908
S2458 Clonidine HCl Clonidine HCl is a direct-acting α2 adrenergic agonist with an ED50 of 0.02±0.01 mg/kg.
S2475 Imatinib (STI571) Imatinib (STI571, CGP057148B, Gleevec) is a multi-target inhibitor of tyrosine kinase with inhibition for v-Abl, c-Kit and PDGFR, IC50 values are 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. Imatinib (STI571) induces autophagy.
Cell Host Microbe, 2021, 29(6):941-958.e10
Nat Commun, 2021, 12(1):51
Clin Cancer Res, 2021, 27(9):2533-2548
S2476 Itraconazole (R 51211) Itraconazole (R 51211) is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. Itraconazole is a potent antagonist of the Hedgehog (Hh) signaling pathway. Itraconazole suppresses the growth of glioblastoma through induction of autophagy.
Nat Biotechnol, 2021, 10.1038/s41587-021-00860-4
Sci Rep, 2021, 11(1):17665
Front Microbiol, 2021, 12:649026
S2480 Loperamide HCl Loperamide HCl (ADL 2-1294) is a selective μ-opioid receptor agonist opioid with Ki of 3.3 nM, 15-fold and 350-fold selective over the δ subtype and the κ subtype of the opioid receptor, used against diarrhea resulting from gastroenteritis or inflammatory bowel disease.
bioRxiv, 2020, 2020/9/20.4.7.30734
Exp Ther Med, 2019, 17(2):1312-1320
Nutrients, 2017, 9(12)
S2491 Nitrendipine Nitrendipine (Bayotensin) is a dihydropyridine calcium channel blocker with an IC50 of 95 nM.
S2505 Rosiglitazone (BRL-49653) maleate Rosiglitazone maleate (BRL 49653), a member of the thiazolidinedione class of antihyperglycaemic agents, is a high-affinity selective agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ) with IC50 of 42 nM. Rosiglitazone maleate also modulates TRP channels and induces autophagy. Rosiglitazone prevents ferroptosis.
Cell Death Dis, 2021, 12(11):972
Antioxidants (Basel), 2021, 10(2)155
Front Cardiovasc Med, 2021, 8:698056
S2556 Rosiglitazone (BRL 49653) Rosiglitazone (BRL 49653) is a potent antihyperglycemic agent and a potent thiazolidinedione insulin sensitizer with IC50 of 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha-binding action. Rosiglitazone modulates TRP channels and induces autophagy. Rosiglitazone prevents ferroptosis.
Toxicology, 2022, 465:153048
Sci Adv, 2021, 7(35)eabj0364
Cell Death Dis, 2021, 12(11):972
S2606 Mifepristone (RU486) Mifepristone (RU486, C-1073, RU 38486, Mifegyne) is a remarkably active antagonist of progesterone receptor and glucocorticoid receptor with IC50 of 0.2 nM and 2.6 nM, respectively. Mifepristone promotes cell autophagy and apoptosis, decreases Bcl-2 level and increases Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1.
Nat Commun, 2021, 12(1):7041
Exp Eye Res, 2021, S0014-4835(21)00331-6
Oncol Rep, 2021, 46(3)202
S2619 MG-132 MG132 (Z-Leu-Leu-Leu-al) is a potent cell-permeable proteasome and calpain inhibitor with IC50s of 0.1 μM and 1.2 μM for the inhibition of proteasome and calpain, respectively. MG132 activates autophagy and induces apoptosis in tumor cells.
Theranostics, 2022, 12(2):976-998
FASEB J, 2022, 36(1):e22087
Biomed Pharmacother, 2022, 145:112432
S2624 OSI-027 OSI-027 (ASP4786, CERC 006, AEVI-006) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM in cell-free assays, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. OSI-027 induces autophagy in cancer cells. Phase 1.
Cell Death Discov, 2021, 7(1):201
Mol Ther Nucleic Acids, 2020, 1;20:801-811
Proc Natl Acad Sci U S A, 2019, 10.1073/pnas.1911393116
S2626 Rabusertib (LY2603618) Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.
Nat Genet, 2021, 10.1038/s41588-021-00893-0
Cancer Cell, 2021, S1535-6108(21)00383-4
Nucleic Acids Res, 2021, gkab643
S2635 CCT128930 CCT128930 is a potent, ATP-competitive and selective inhibitor of Akt2 with IC50 of 6 nM in a cell-free assay, 28-fold greater selectivity for Akt2 than the closely related PKA kinase. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. High dose of CCT128930 triggers cell apoptosis in HepG2 cells.
ACS Nano, 2021, 10.1021/acsnano.1c06452
Front Pharmacol, 2020, 11:593832
Biomed Pharmacother, 2020, 130:110544
S2658 Omipalisib (GSK2126458) Omipalisib (GSK2126458, GSK458) is a highly selective and potent inhibitor of p110α/β/δ/γ, mTORC1/2 with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM in cell-free assays, respectively. Omipalisib induces autophagy. Phase 1.
Cell Metab, 2021, S1550-4131(21)00326-0
Cancer Res, 2021, canres.3199.2020
Mol Cancer Res, 2021, molcanres.0301.2021
S2673 Trametinib (GSK1120212) Trametinib (GSK1120212, JTP-74057, Mekinist) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis.
Nature, 2021, 10.1038/s41586-021-03916-2
Cell, 2021, 184(25):6119-6137.e26
Nat Biotechnol, 2021, 10.1038/s41587-021-00837-3
S2679 Flavopiridol (L86-8275) HCl Flavopiridol HCl (L86-8275, NSC 649890, Alvocidib, HMR-1275, DSP-2033) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM in cell-free assays. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol HCl induces autophagy and ER stress. Flavopiridol HCl blocks HIV-1 replication. Phase 1/2.
Nature, 2021, 10.1038/s41586-021-03445-y
Genome Res, 2021, 31(6):981-994
EMBO Rep, 2021, e52023
S2696 Apitolisib (GDC-0980) Apitolisib (GDC-0980, RG7422, GNE 390) is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively. Also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases. Apitolisib activates autophagy and apoptosis simultaneously in pancreatic cancer cells. Phase 2.
Adv Sci (Weinh), 2021, e2103360
Cancers (Basel), 2021, 13(9)2139
Commun Biol, 2021, 4(1):1333
S2713 Geldanamycin (NSC 122750) Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.
Cell Chem Biol, 2021, S2451-9456(21)00221-X
J Virol, 2021, JVI0059421
Int J Pharm, 2021, 610:121272
S2751 Milciclib (PHA-848125) Milciclib (PHA-848125) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Milciclib (PHA-848125) induces cell death through autophagy. Phase 2.
Sci Rep, 2021, 11(1):7259
Eur J Pharm Sci, 2021, 159:105740
Eur J Pharm Sci, 2021, S0928-0987(21)00042-7
S2770 MK-5108 (VX-689) MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) induces autophagy. Phase 1.
Cancer Cell, 2021, S1535-6108(21)00383-4
Adv Sci (Weinh), 2021, e2103360
Anal Chem, 2021, 93(30):10653-10660
S2782 GW4064 GW4064 is an agonist of farnesoid X receptor (FXR) with EC50 of 65 nM in CV1 cell line and displays no activity at other nuclear receptors at concentrations up to 1 μM. GW4064 stimulates autophagy in MCF-7 cells.
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Theranostics, 2020, 10(23):10434-10447
J Neuroinflammation, 2020, 25;17(1):164
S2783 Vistusertib (AZD2014) Vistusertib (AZD2014) is a novel mTOR inhibitor with IC50 of 2.8 nM in a cell-free assay; highly selective against multiple PI3K isoforms (α/β/γ/δ). AZD2014 showed no or weak binding to the majority of kinases when tested at 1 μM. AZD2014 induces proliferation suppression, apoptosis, cell cycle arrest, and autophagy in HCC cells with antitumor activity.
Adv Sci (Weinh), 2021, e2103360
Nat Commun, 2021, 12(1):1876
Cell Rep, 2021, 35(1):108940
S2799 Daporinad (FK866, APO866) Daporinad (FK866, APO866) effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase; Nampt) with IC50 of 0.09 nM in a cell-free assay. Daporinad (FK866, APO866) triggers autophagy. Phase 1/2.
Cancer Cell, 2021, S1535-6108(21)00338-X
Cell Metab, 2021, 33(1):110-127.e5
Free Radic Biol Med, 2021, 162:514-522
S2812 (R)-(-)-Gossypol acetic acid (R)-(-)-Gossypol (AT-101) acetic acid, the R-(-) enantiomer of Gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.32 μM, 0.48 μM and 0.18 μM in cell-free assays; does not inhibit BIR3 domain and BID. AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy. Phase 2.
Eur J Pharm Sci, 2020, 142:105105
Platelets, 2020, 10.1080/09537104.2020.1724276
Cancers (Basel), 2020, 12(8):E2298
S2817 Torin 2 Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis.
Nat Commun, 2021, 12(1):245
Cell Rep, 2021, 35(1):108940
Cell Death Dis, 2021, 12(11):1028
S2827 Torin 1 Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.
Cell Metab, 2021, S1550-4131(21)00326-0
Mol Cell, 2021, S1097-2765(21)00736-X
Nat Commun, 2021, 12(1):4789
S2843 BI-D1870 BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. BI-D1870 exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.
EMBO J, 2021, 40(7):e106106
Cell Rep, 2021, 37(12):110137
J Med Chem, 2021, 64(18):13572-13587