Bcl-2

Bcl-2 Products

  • All (57)
  • Bcl-2 Inhibitors (38)
  • Bcl-2 Activators (8)
  • Bcl-2 Antagonists (5)
  • Bcl-2 Modulators (5)
  • New Bcl-2 Products
Catalog No. Product Name Information Product Use Citations Product Validations
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.
Nat Commun, 2024, 15(1):1821
Cell Death Dis, 2024, 15(2):131
Cell Death Discov, 2024, 10(1):35
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.
Gastroenterology, 2024, S0016-5085(24)00062-3
Nat Commun, 2024, 15(1):830
Nat Commun, 2024, 15(1):1041
S1001 Navitoclax (ABT-263) Navitoclax (ABT-263) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2.
Gastroenterology, 2024, S0016-5085(24)00062-3
Nat Commun, 2024, 15(1):1041
Theranostics, 2024, 14(3):1224-1240
S7747 Ro-3306 RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases. RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis.
Haematologica, 2024, 109(1):231-244
bioRxiv, 2024, 2024.01.17.575938
Nat Commun, 2023, 14(1):6322
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.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Emerg Microbes Infect, 2022, 1-29
Cancers (Basel), 2022, 14(22)5602
S8383 S63845 S63845 is a new, selective MCL-1 inhibitor with the Kd value of 0.19 nM and has no discernible binding to the other BCL-2 members, BCL-2 or BCL-XL.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Nat Commun, 2023, 14(1):1399
Nat Commun, 2023, 14(1):1399
S7790 A-1210477 A-1210477 is a potent and selective MCL-1 inhibitor with Ki and IC50 of 0.454 nM and 26.2 nM, respectively, >100-fold selectivity over other Bcl-2 family members.
Cell Rep, 2023, 42(10):113176
Int J Mol Sci, 2023, 24(13)11149
Int J Mol Sci, 2023, 24(13)11149
S1121 TW-37 TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM in cell-free assays, respectively.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
S7801 A-1331852 A-1331852 is a potent and selectiveBCL-XL inhibitor with Ki value less than 0.01 nM for BCL-XL and 6 nM, 4 nM, 142 nM for Bcl-2, Bcl-W, MCL-1 respectively. It may be useful in the treatment of cancer, immune and autoimmune diseases.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Nat Commun, 2023, 14(1):4033
Nat Commun, 2023, 14(1):1461
S7800 A-1155463 Dihydrochloride A-1155463 Dihydrochloride, a highly potent and selective BCL-XL inhibitor, shows picomolar binding affinity to BCL-XL, and >1000-fold weaker binding to BCL-2 and related proteins BCL-W(Ki=19 nM) and MCL-1(Ki>440 nM).
Nat Commun, 2023, 14(1):4033
Cell Death Dis, 2023, 14(2):102
Clin Cancer Res, 2023, 29(16):3151-3161
S2606 Mifepristone Mifepristone 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.
Cell Death Dis, 2024, 15(1):70
Oncogene, 2024, 43(4):235-247
Neurobiol Stress, 2024, 28:100593
S7531 UMI-77 UMI-77 is a selective Mcl-1 inhibitor with Ki of 490 nM, showing selectivity over other members of Bcl-2 family.
Blood, 2022, blood.2021014304
Nat Commun, 2022, 13(1):6226
Nat Commun, 2022, 13(1):6226
S2812 (R)-(-)-Gossypol (AT-101) 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.
Int J Mol Sci, 2023, 24(7)6662
Cancer Cell, 2022, S1535-6108(22)00312-9
Front Oncol, 2022, 12:821620
S8643 AZD5991 AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of AZD5991 is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.
Cell Rep, 2023, 42(10):113176
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
S8061 Sabutoclax Sabutoclax (BI-97C1) is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Mol Divers, 2022, 10.1007/s11030-022-10494-6
S7100 WEHI-539 WEHI-539 has high affinity (IC50=1.1 nM) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. It has more than a 400-fold higher affinity for BCL-XL versus other prosurvival BCL-2 family members.
Liver Int, 2022, 10.1111/liv.15392
Cell Death Differ, 2021, 10.1038/s41418-021-00816-w
Commun Biol, 2021, 4(1):20
S1071 HA14-1 HA14-1 is a non-peptidic ligand of a Bcl-2 surface pocket with IC50 of ~9 μM.
Platelets, 2020, 10.1080/09537104.2020.1724276
Oncotarget, 2018, 9(24):16701-16717
Oncotarget, 2015, 6(34):36113-25
S8836 MIK665 (S64315) MIK665 (S64315) is an inhibitor of induced myeloid leukemia cell differentiation protein Mcl-1 with Ki value of 1.2 nM and has potential pro-apoptotic and antineoplastic activities.
Nat Commun, 2024, 15(1):1581
Cell Rep, 2023, 42(10):113176
Biomedicines, 2023, 11(6)1666
S6709 Obatoclax (GX15-070)

Obatoclax (GX15-070) is an antagonist of Bcl-2 with an Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis.

Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Int J Mol Sci, 2023, 24(7)6662
S8820 Unesbulin (PTC596) Unesbulin (PTC596) is a second-generation BMI-1 inhibitor that accelerates BMI-1 degradation. PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis. IC50 values at 72 hours ranged from 68 to 340 nM in mantle cell lymphoma (MCL) cell lines.
PLoS One, 2023, 18(2):e0277313
bioRxiv, 2023, 2023.01.23.525196
Cell Death Dis, 2021, 12(5):495
S2448 Gambogic Acid Gambogic Acid (Guttatic Acid, Guttic Acid, Beta-Guttiferrin) activates caspases with EC50 of 0.78-1.64 μM and competitively inhibits Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 with IC50 of 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 μM, respectively.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Cancers (Basel), 2022, 14(22)5505
S7126 Marinopyrrole A (Maritoclax) Marinopyrrole A (Maritoclax) is a selective Mcl-1 antagonist. It binds to Mcl-1, but not Bcl-XL, and targets Mcl-1 for proteasomal degradation. Maritoclax disrupts the interaction between Bim and Mcl-1 with an IC50 of 10.1 μM.
Clin Cancer Res, 2023, 29(2):446-457
Cell Signal, 2022, S0898-6568(22)00041-9
Leukemia, 2019, 33(2):319-332
S8865 BAI1 BAI1 is a direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM.
Nat Commun, 2023, 14(1):865
iScience, 2022, 25(10):105145
Cell Rep Methods, 2022, 2(3)100174
S6852 Gossypol Gossypol (BL 193) is an orally-active polyphenol isolated from cotton seeds and roots. Gossypol is a potent inhibitor of 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase with IC50 of 3.33 μM and 0.52 μM in cell-free assay, respectively. Gossypol also inhibits the binding of BH3 peptide to Bcl protein with IC50 of 0.4 μM and 10 μM for Bcl-XL and Bcl-2, respectively. Gossypol induces apoptosis and cell growth inhibition in various cancer cells.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Mol Med Rep, 2021, 23(1)40
E2926New A-1155463 A-1155463 is a highly potent and selective BCL-XL inhibitor with EC50 of 65 nM in H146 cells.
Nat Commun, 2023, 14(1):4033
Clin Cancer Res, 2023, 29(16):3151-3161
Cell Death Dis, 2023, 14(9):600
S8650 BTSA1 BTSA1 is a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Cell Mol Life Sci, 2023, 80(10):311
Cell Death Dis, 2021, 12(11):1050
S8759 S55746 S55746 (S 055746,BCL201) is a novel, orally active BCL-2 specific inhibitor (Ki = 1.3 nM) with poor affinity for BCL-XL and no significant binding to MCL-1, BFL-1 (BCL2A1/A1). The selectivity of S55746 for BCL-2 versus BCL-XL ranges from ~70 to 400 folds.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Signal Transduct Target Ther, 2022, 7(1):51
S7105 BAM7 BAM 7 is a direct and selective activator of proapoptotic Bax with EC50 of 3.3 μM.
Nat Chem Biol, 2019, 15(4):322-330
Cell Death Discov, 2018, 4:107
S3275 Senkyunolide I Senkyunolide I (SEI, SENI) is an orally active compound isolated from Ligusticum chuanxiong with analgesic, anti-migraine, neuroprotective, anti-oxidation and anti-apoptosis activities. Senkyunolide I (SEI, SENI) up-regulates the phosphorylation of Erk1/2 and induces Nrf2 nuclear translocation with enhanced HO-1 and NQO1 expressions. Senkyunolide I (SEI, SENI) promotes the ratio of Bcl-2/Bax and inhibits the expressions of cleaved caspase 3 and caspase 9.
SSRN , 2024, 10.2139/ssrn.4696834
Cancer Biol Med, 2022, 19(11)j.issn.2095-3941.2022.0451
Cell Commun Signal, 2021, 19(1):115
S5967 Berberine chloride hydrate Berberine (Natural Yellow 18) chloride hydrate 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 Biosci (Landmark Ed), 2022, 27(8):242
Front Pharmacol, 2021, 12:632201
S8199 Ruxotemitide (LTX 315) Ruxotemitide (LTX 315) is the oncolytic peptide that kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.
J Immunother Cancer, 2022, 10(3)e004129
Nat Metab, 2021, 10.1038/s42255-021-00491-8
S7849 BDA-366 BDA-366 is a small-molecule Bcl2-BH4 domain antagonist and binds BH4 with high affinity and selectivity. It directly binds to Bcl2 with high binding affinity (Ki =3.3 ± 0.73 nM).
BMC Cancer, 2023, 23(1):479
S3238 Resibufogenin Resibufogenin (Bufogenin, Recibufogenin), a component of huachansu with anticancer effect, triggers necroptosis through upregulating receptor-interacting protein kinase 3 (RIP3) and phosphorylating mixed lineage kinase domain-like protein at Ser358. Resibufogenin exerts cytotoxic effect by inducing reactive oxygen species (ROS) accumulation. Resibufogenin induces apoptosis and caspase-3 and caspase-8 activity. Resibufogenin increases Bax/Bcl-2 expression, and suppresses cyclin D1, cyclin E, PI3K, p-AKT, p-GSK3β and β-catenin protein expression.
Research Square, 2024, 10.21203/rs.3.rs-3790060/v1
Phytomedicine, 2022, 102:154182
S0563 10-Deacetyl-7-xylosyl paclitaxel 10-Deacetyl-7-xylosyl paclitaxel (10-Deacetyl-7-xylosyltaxol, 7-xylosyl-10-deacetylpaclitaxel), a derivative of paclitaxel and naturally occurring xyloside isolated from Taxus chinensis, causes significant mitotic arrest in PC-3 cells followed by up-regulating expression of pro-apoptotic Bax and Bad protein, as well as down-regulating expression of anti-apoptotic Bcl-2 and Bcl-XL , which leads to a disturbance of the mitochondrial membrane permeability and to the activation of caspase-9.
Cell Death Dis, 2022, 13-9:799
S6990 Phytohemagglutinin

Phytohemagglutinin (PHA, Phaseolus vulgaris agglutinin) is expressed in Pichia pastoris using native signal peptides, or the Saccharomyces alpha-factor preprosequence, to direct proteins into the secretory pathway. Phytohemagglutinin induces apoptosis in human HEp-2 carcinoma cells via increasing proapoptotic protein Bax and activating caspases-3.

Molecules, 2023, 28(6)2426
E0124 Chelerythrine

Chelerythrine (Toddaline, Broussonpapyrine) is a potent, selective antagonist of PKC with an IC50 of 0.66 μM. Chelerythrine also inhibits the BclXL-Bak BH3 peptide binding with an IC50 of 1.5 μM. Chelerythrine shows antitumor, antidiabetic and anti-inflammatory activity.

Nutr Neurosci, 2022, 1-19
E3037 Solanum lyratum Extract Solanum lyratum Extract (300 μg/ml) increases Bax levels and decreases Bcl-2 levels, which cause the loss of mitochondrial membrane potential (Δæm) followed by cytochrome C release and caspase-9 and -3 activation, finally leading to apoptosis. Solanum lyratum Extract (300 μg/ml) also promotes p53 and p27, but decreases the levels of cyclin B1 thus causing S-phase arrest.
S3224 Cinobufagin Cinobufagin (Cinobufagine), an active ingredient of Venenum Bufonis, inhibits tumor development. Cinobufagin increases ATM and Chk2 and decreases CDC25C, CDK1, and cyclin B. Cinobufagin inhibits PI3K, AKT and Bcl-2 while increases levels of cleaved caspase-9 and caspase-3. Thus, Cinobufagin induces cell cycle arrest at the G2/M phase and apoptosis.
S6895 TCPOBOP TCPOBOP is a constitutive androstane receptor (CAR) agonist. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
S9970 APG-2575 (lisaftoclax) APG-2575 (lisaftoclax) is a dual Bcl-2 and Bcl-xl inhibitor with IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively.
S3245 Nodakenetin Nodakenetin (NANI), a plant-derived coumarin isolated from Angelica decursiva, inhibits α-glucosidase, PTP1B, rat lens aldose reductase (RLAR), AChE, BChE, and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Nodakenetin alters the protein expression of Bax and Bcl-2, and prompts mitochondrial apoptosis. Nodakenetin exhibits anti-tumor activity.
S3267 Nicotiflorin (Kaempferol-3-O-rutinoside) Nicotiflorin (Kaempferol-3-O-rutinoside), a flavonoid extracted from Carthamus tinctorius, alters the shape and structure of injured neurons, decreases the number of apoptotic cells, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax and decreases Bax immunoredactivity, and increases Bcl-2 protein expression and immunoreactivity.
S3243 Zeaxanthin Zeaxanthin, the carotenoid alcohol participates in the xanthophyll cycle, activates the extrinsic apoptosis pathway which induces apoptosis on uveal melanoma cells with IC50 value 40.8 µM.
E2354 Valepotriate Valepotriate, an unstable iridoid isolated from Valeriana jatamansi Jones, has anti-epileptic by significantly increasing the expression of GABAA, glutamic acid decarboxylase 65, and Bcl-2 and reduce the expression of caspase-3.
E2028 Humanin Humanin (human) (1-24-Protein humanin (human)), a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA, exhibits protective effects in several cell types against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein.
E0011 Linderalactone Linderalactone inhibits human lung cancer growth by modulating the expression of apoptosis-related proteins (Bax and Bcl-2) with an IC50 of 15 µM in A-549 cells. Linderalactone induces G2/M cell cycle arrest and could also suppress the JAK/STAT signalling pathway. Linderalactone can be isolated from Radix linderae.
S9276 Alisol B Alisol B, a triterpene from Alismatis rhizoma, induces Bax up-regulation and nuclear translocation, the activation of initiator caspase-8 and caspase-9, and executor caspase-3, suggesting the involvement of both extrinsic and intrinsic apoptosis pathways.
S2271 Berberine chloride Berberine chloride 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.
Adv Healthc Mater, 2023, e2300591.
Transl Oncol, 2023, 35:101712
J Biomol Struct Dyn, 2022, 1-11
S5600 Flavokawain A Flavokawain A, extracted from kava, is an apoptotic inducers and anticarcinogenic agent. Flavokawain A can down-regulation of antiapoptotic proteins, such as XIAP, survivin, and Bcl-xL, thereby changing the balance between apoptotic and antiapoptotic molecules and then induce cell death in tumor cells.
S8177 BH3I-1 BH3I-1 is a Bcl-XL-BH3 domain interaction inhibitor with Ki of 2.4 μM (by fluorescence polarization ).It is a selective inhibitor of Bcl-2 family proteins.
S8924 DT2216 DT2216 is a potent and selective degrader of BCL-XL based on PROTAC technology. DT2216 inhibits various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets.
S6004 CCI-007 CCI-007 is a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements.
S9665 Motixafortide (BL-8040) Motixafortide (BL-8040, BKT140, TF 14016, 4-fluorobenzoyl, 4F-benzoyl-TN14003, T140) is an antagonist of CXCR4 with IC50 of ~1 nM. BL-8040 induces the apoptosis of AML blasts by down-regulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression.
S8758 VU661013 VU661013 is a novel, potent, selective MCL1 inhibitor with Ki of 97 ± 30 pM of human MCL-1 in a TR-FRET assay. However, VU661013 does not significantly inhibit BCL-xL or BCL-2 with Ki > 40 μM or = 0.73 μM. VU661013 de-stabilizes BIM/MCL-1 association, leads to apoptosis in AML.
S5550 Ethyl gallate Ethyl gallat (Phyllemblin, gallic acid ethyl ester), which could be found naturally in a variety of plant sources, is a food additive with antimicrobial activity. Ethyl gallat activates the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid).
E2663 BT2 BT2 is a novel branched-chain α-ketoacid dehydrogenase complex kinase (BDK) inhibitor wieh an IC50 of 3.19 μM.
E3020 Hedyotic Diffusa Extract Hedyotic Diffusa Extract is extracted from Hedyotic diffusa, of which polysaccharides inhibit the growth of CNE2 cells in a dose-and-time-dependent way, the mechanism may involve induction of cell apoptosis, which is associated with the activation of Bax and caspase-3 protein and the down-regulation of Bcl-2 protein expression.
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.
Nat Commun, 2024, 15(1):1821
Cell Death Dis, 2024, 15(2):131
Cell Death Discov, 2024, 10(1):35
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.
Gastroenterology, 2024, S0016-5085(24)00062-3
Nat Commun, 2024, 15(1):830
Nat Commun, 2024, 15(1):1041
S1001 Navitoclax (ABT-263) Navitoclax (ABT-263) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2.
Gastroenterology, 2024, S0016-5085(24)00062-3
Nat Commun, 2024, 15(1):1041
Theranostics, 2024, 14(3):1224-1240
S8383 S63845 S63845 is a new, selective MCL-1 inhibitor with the Kd value of 0.19 nM and has no discernible binding to the other BCL-2 members, BCL-2 or BCL-XL.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Nat Commun, 2023, 14(1):1399
Nat Commun, 2023, 14(1):1399
S7790 A-1210477 A-1210477 is a potent and selective MCL-1 inhibitor with Ki and IC50 of 0.454 nM and 26.2 nM, respectively, >100-fold selectivity over other Bcl-2 family members.
Cell Rep, 2023, 42(10):113176
Int J Mol Sci, 2023, 24(13)11149
Int J Mol Sci, 2023, 24(13)11149
S1121 TW-37 TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM in cell-free assays, respectively.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
S7801 A-1331852 A-1331852 is a potent and selectiveBCL-XL inhibitor with Ki value less than 0.01 nM for BCL-XL and 6 nM, 4 nM, 142 nM for Bcl-2, Bcl-W, MCL-1 respectively. It may be useful in the treatment of cancer, immune and autoimmune diseases.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Nat Commun, 2023, 14(1):4033
Nat Commun, 2023, 14(1):1461
S7800 A-1155463 Dihydrochloride A-1155463 Dihydrochloride, a highly potent and selective BCL-XL inhibitor, shows picomolar binding affinity to BCL-XL, and >1000-fold weaker binding to BCL-2 and related proteins BCL-W(Ki=19 nM) and MCL-1(Ki>440 nM).
Nat Commun, 2023, 14(1):4033
Cell Death Dis, 2023, 14(2):102
Clin Cancer Res, 2023, 29(16):3151-3161
S2606 Mifepristone Mifepristone 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.
Cell Death Dis, 2024, 15(1):70
Oncogene, 2024, 43(4):235-247
Neurobiol Stress, 2024, 28:100593
S7531 UMI-77 UMI-77 is a selective Mcl-1 inhibitor with Ki of 490 nM, showing selectivity over other members of Bcl-2 family.
Blood, 2022, blood.2021014304
Nat Commun, 2022, 13(1):6226
Nat Commun, 2022, 13(1):6226
S2812 (R)-(-)-Gossypol (AT-101) 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.
Int J Mol Sci, 2023, 24(7)6662
Cancer Cell, 2022, S1535-6108(22)00312-9
Front Oncol, 2022, 12:821620
S8643 AZD5991 AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of AZD5991 is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.
Cell Rep, 2023, 42(10):113176
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
S8061 Sabutoclax Sabutoclax (BI-97C1) is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Mol Divers, 2022, 10.1007/s11030-022-10494-6
S1071 HA14-1 HA14-1 is a non-peptidic ligand of a Bcl-2 surface pocket with IC50 of ~9 μM.
Platelets, 2020, 10.1080/09537104.2020.1724276
Oncotarget, 2018, 9(24):16701-16717
Oncotarget, 2015, 6(34):36113-25
S8836 MIK665 (S64315) MIK665 (S64315) is an inhibitor of induced myeloid leukemia cell differentiation protein Mcl-1 with Ki value of 1.2 nM and has potential pro-apoptotic and antineoplastic activities.
Nat Commun, 2024, 15(1):1581
Cell Rep, 2023, 42(10):113176
Biomedicines, 2023, 11(6)1666
S8820 Unesbulin (PTC596) Unesbulin (PTC596) is a second-generation BMI-1 inhibitor that accelerates BMI-1 degradation. PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis. IC50 values at 72 hours ranged from 68 to 340 nM in mantle cell lymphoma (MCL) cell lines.
PLoS One, 2023, 18(2):e0277313
bioRxiv, 2023, 2023.01.23.525196
Cell Death Dis, 2021, 12(5):495
S2448 Gambogic Acid Gambogic Acid (Guttatic Acid, Guttic Acid, Beta-Guttiferrin) activates caspases with EC50 of 0.78-1.64 μM and competitively inhibits Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 with IC50 of 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 μM, respectively.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Cancers (Basel), 2022, 14(22)5505
S8865 BAI1 BAI1 is a direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM.
Nat Commun, 2023, 14(1):865
iScience, 2022, 25(10):105145
Cell Rep Methods, 2022, 2(3)100174
S6852 Gossypol Gossypol (BL 193) is an orally-active polyphenol isolated from cotton seeds and roots. Gossypol is a potent inhibitor of 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase with IC50 of 3.33 μM and 0.52 μM in cell-free assay, respectively. Gossypol also inhibits the binding of BH3 peptide to Bcl protein with IC50 of 0.4 μM and 10 μM for Bcl-XL and Bcl-2, respectively. Gossypol induces apoptosis and cell growth inhibition in various cancer cells.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Mol Med Rep, 2021, 23(1)40
E2926New A-1155463 A-1155463 is a highly potent and selective BCL-XL inhibitor with EC50 of 65 nM in H146 cells.
Nat Commun, 2023, 14(1):4033
Clin Cancer Res, 2023, 29(16):3151-3161
Cell Death Dis, 2023, 14(9):600
S8759 S55746 S55746 (S 055746,BCL201) is a novel, orally active BCL-2 specific inhibitor (Ki = 1.3 nM) with poor affinity for BCL-XL and no significant binding to MCL-1, BFL-1 (BCL2A1/A1). The selectivity of S55746 for BCL-2 versus BCL-XL ranges from ~70 to 400 folds.
Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Signal Transduct Target Ther, 2022, 7(1):51
S5967 Berberine chloride hydrate Berberine (Natural Yellow 18) chloride hydrate 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 Biosci (Landmark Ed), 2022, 27(8):242
Front Pharmacol, 2021, 12:632201
E0124 Chelerythrine

Chelerythrine (Toddaline, Broussonpapyrine) is a potent, selective antagonist of PKC with an IC50 of 0.66 μM. Chelerythrine also inhibits the BclXL-Bak BH3 peptide binding with an IC50 of 1.5 μM. Chelerythrine shows antitumor, antidiabetic and anti-inflammatory activity.

Nutr Neurosci, 2022, 1-19
S3224 Cinobufagin Cinobufagin (Cinobufagine), an active ingredient of Venenum Bufonis, inhibits tumor development. Cinobufagin increases ATM and Chk2 and decreases CDC25C, CDK1, and cyclin B. Cinobufagin inhibits PI3K, AKT and Bcl-2 while increases levels of cleaved caspase-9 and caspase-3. Thus, Cinobufagin induces cell cycle arrest at the G2/M phase and apoptosis.
S6895 TCPOBOP TCPOBOP is a constitutive androstane receptor (CAR) agonist. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
S9970 APG-2575 (lisaftoclax) APG-2575 (lisaftoclax) is a dual Bcl-2 and Bcl-xl inhibitor with IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively.
S3243 Zeaxanthin Zeaxanthin, the carotenoid alcohol participates in the xanthophyll cycle, activates the extrinsic apoptosis pathway which induces apoptosis on uveal melanoma cells with IC50 value 40.8 µM.
E2354 Valepotriate Valepotriate, an unstable iridoid isolated from Valeriana jatamansi Jones, has anti-epileptic by significantly increasing the expression of GABAA, glutamic acid decarboxylase 65, and Bcl-2 and reduce the expression of caspase-3.
E0011 Linderalactone Linderalactone inhibits human lung cancer growth by modulating the expression of apoptosis-related proteins (Bax and Bcl-2) with an IC50 of 15 µM in A-549 cells. Linderalactone induces G2/M cell cycle arrest and could also suppress the JAK/STAT signalling pathway. Linderalactone can be isolated from Radix linderae.
S2271 Berberine chloride Berberine chloride 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.
Adv Healthc Mater, 2023, e2300591.
Transl Oncol, 2023, 35:101712
J Biomol Struct Dyn, 2022, 1-11
S5600 Flavokawain A Flavokawain A, extracted from kava, is an apoptotic inducers and anticarcinogenic agent. Flavokawain A can down-regulation of antiapoptotic proteins, such as XIAP, survivin, and Bcl-xL, thereby changing the balance between apoptotic and antiapoptotic molecules and then induce cell death in tumor cells.
S8177 BH3I-1 BH3I-1 is a Bcl-XL-BH3 domain interaction inhibitor with Ki of 2.4 μM (by fluorescence polarization ).It is a selective inhibitor of Bcl-2 family proteins.
S8924 DT2216 DT2216 is a potent and selective degrader of BCL-XL based on PROTAC technology. DT2216 inhibits various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets.
S6004 CCI-007 CCI-007 is a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements.
S9665 Motixafortide (BL-8040) Motixafortide (BL-8040, BKT140, TF 14016, 4-fluorobenzoyl, 4F-benzoyl-TN14003, T140) is an antagonist of CXCR4 with IC50 of ~1 nM. BL-8040 induces the apoptosis of AML blasts by down-regulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression.
S8758 VU661013 VU661013 is a novel, potent, selective MCL1 inhibitor with Ki of 97 ± 30 pM of human MCL-1 in a TR-FRET assay. However, VU661013 does not significantly inhibit BCL-xL or BCL-2 with Ki > 40 μM or = 0.73 μM. VU661013 de-stabilizes BIM/MCL-1 association, leads to apoptosis in AML.
E2663 BT2 BT2 is a novel branched-chain α-ketoacid dehydrogenase complex kinase (BDK) inhibitor wieh an IC50 of 3.19 μM.
E3020 Hedyotic Diffusa Extract Hedyotic Diffusa Extract is extracted from Hedyotic diffusa, of which polysaccharides inhibit the growth of CNE2 cells in a dose-and-time-dependent way, the mechanism may involve induction of cell apoptosis, which is associated with the activation of Bax and caspase-3 protein and the down-regulation of Bcl-2 protein expression.
S7747 Ro-3306 RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases. RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis.
Haematologica, 2024, 109(1):231-244
bioRxiv, 2024, 2024.01.17.575938
Nat Commun, 2023, 14(1):6322
S8650 BTSA1 BTSA1 is a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Cell Mol Life Sci, 2023, 80(10):311
Cell Death Dis, 2021, 12(11):1050
S7105 BAM7 BAM 7 is a direct and selective activator of proapoptotic Bax with EC50 of 3.3 μM.
Nat Chem Biol, 2019, 15(4):322-330
Cell Death Discov, 2018, 4:107
S3275 Senkyunolide I Senkyunolide I (SEI, SENI) is an orally active compound isolated from Ligusticum chuanxiong with analgesic, anti-migraine, neuroprotective, anti-oxidation and anti-apoptosis activities. Senkyunolide I (SEI, SENI) up-regulates the phosphorylation of Erk1/2 and induces Nrf2 nuclear translocation with enhanced HO-1 and NQO1 expressions. Senkyunolide I (SEI, SENI) promotes the ratio of Bcl-2/Bax and inhibits the expressions of cleaved caspase 3 and caspase 9.
SSRN , 2024, 10.2139/ssrn.4696834
Cancer Biol Med, 2022, 19(11)j.issn.2095-3941.2022.0451
Cell Commun Signal, 2021, 19(1):115
S3238 Resibufogenin Resibufogenin (Bufogenin, Recibufogenin), a component of huachansu with anticancer effect, triggers necroptosis through upregulating receptor-interacting protein kinase 3 (RIP3) and phosphorylating mixed lineage kinase domain-like protein at Ser358. Resibufogenin exerts cytotoxic effect by inducing reactive oxygen species (ROS) accumulation. Resibufogenin induces apoptosis and caspase-3 and caspase-8 activity. Resibufogenin increases Bax/Bcl-2 expression, and suppresses cyclin D1, cyclin E, PI3K, p-AKT, p-GSK3β and β-catenin protein expression.
Research Square, 2024, 10.21203/rs.3.rs-3790060/v1
Phytomedicine, 2022, 102:154182
S6990 Phytohemagglutinin

Phytohemagglutinin (PHA, Phaseolus vulgaris agglutinin) is expressed in Pichia pastoris using native signal peptides, or the Saccharomyces alpha-factor preprosequence, to direct proteins into the secretory pathway. Phytohemagglutinin induces apoptosis in human HEp-2 carcinoma cells via increasing proapoptotic protein Bax and activating caspases-3.

Molecules, 2023, 28(6)2426
S9276 Alisol B Alisol B, a triterpene from Alismatis rhizoma, induces Bax up-regulation and nuclear translocation, the activation of initiator caspase-8 and caspase-9, and executor caspase-3, suggesting the involvement of both extrinsic and intrinsic apoptosis pathways.
S5550 Ethyl gallate Ethyl gallat (Phyllemblin, gallic acid ethyl ester), which could be found naturally in a variety of plant sources, is a food additive with antimicrobial activity. Ethyl gallat activates the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid).
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.
bioRxiv, 2024, 10.1101/2023.01.18.524628
Emerg Microbes Infect, 2022, 1-29
Cancers (Basel), 2022, 14(22)5602
S7100 WEHI-539 WEHI-539 has high affinity (IC50=1.1 nM) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. It has more than a 400-fold higher affinity for BCL-XL versus other prosurvival BCL-2 family members.
Liver Int, 2022, 10.1111/liv.15392
Cell Death Differ, 2021, 10.1038/s41418-021-00816-w
Commun Biol, 2021, 4(1):20
S6709 Obatoclax (GX15-070)

Obatoclax (GX15-070) is an antagonist of Bcl-2 with an Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis.

Cells, 2023, 12(18)2247
Cells, 2023, 10.3390/cells12182247
Int J Mol Sci, 2023, 24(7)6662
S7126 Marinopyrrole A (Maritoclax) Marinopyrrole A (Maritoclax) is a selective Mcl-1 antagonist. It binds to Mcl-1, but not Bcl-XL, and targets Mcl-1 for proteasomal degradation. Maritoclax disrupts the interaction between Bim and Mcl-1 with an IC50 of 10.1 μM.
Clin Cancer Res, 2023, 29(2):446-457
Cell Signal, 2022, S0898-6568(22)00041-9
Leukemia, 2019, 33(2):319-332
S7849 BDA-366 BDA-366 is a small-molecule Bcl2-BH4 domain antagonist and binds BH4 with high affinity and selectivity. It directly binds to Bcl2 with high binding affinity (Ki =3.3 ± 0.73 nM).
BMC Cancer, 2023, 23(1):479
S8199 Ruxotemitide (LTX 315) Ruxotemitide (LTX 315) is the oncolytic peptide that kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.
J Immunother Cancer, 2022, 10(3)e004129
Nat Metab, 2021, 10.1038/s42255-021-00491-8
S0563 10-Deacetyl-7-xylosyl paclitaxel 10-Deacetyl-7-xylosyl paclitaxel (10-Deacetyl-7-xylosyltaxol, 7-xylosyl-10-deacetylpaclitaxel), a derivative of paclitaxel and naturally occurring xyloside isolated from Taxus chinensis, causes significant mitotic arrest in PC-3 cells followed by up-regulating expression of pro-apoptotic Bax and Bad protein, as well as down-regulating expression of anti-apoptotic Bcl-2 and Bcl-XL , which leads to a disturbance of the mitochondrial membrane permeability and to the activation of caspase-9.
Cell Death Dis, 2022, 13-9:799
S3245 Nodakenetin Nodakenetin (NANI), a plant-derived coumarin isolated from Angelica decursiva, inhibits α-glucosidase, PTP1B, rat lens aldose reductase (RLAR), AChE, BChE, and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Nodakenetin alters the protein expression of Bax and Bcl-2, and prompts mitochondrial apoptosis. Nodakenetin exhibits anti-tumor activity.
S3267 Nicotiflorin (Kaempferol-3-O-rutinoside) Nicotiflorin (Kaempferol-3-O-rutinoside), a flavonoid extracted from Carthamus tinctorius, alters the shape and structure of injured neurons, decreases the number of apoptotic cells, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax and decreases Bax immunoredactivity, and increases Bcl-2 protein expression and immunoreactivity.
E2028 Humanin Humanin (human) (1-24-Protein humanin (human)), a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA, exhibits protective effects in several cell types against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein.
E2926New A-1155463 A-1155463 is a highly potent and selective BCL-XL inhibitor with EC50 of 65 nM in H146 cells.
Nat Commun, 2023, 14(1):4033
Clin Cancer Res, 2023, 29(16):3151-3161
Cell Death Dis, 2023, 14(9):600

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