Bcl-2

Choose Selective Bcl-2 Inhibitors

Bcl-2 Signaling Pathway Map

Bcl-2 Signaling Pathways

Bcl-2 Products

  • All (47)
  • Bcl-2 Inhibitors (28)
  • Bcl-2 Activators (8)
  • Bcl-2 Antagonists (6)
  • Bcl-2 Agonist (1)
  • Bcl-2 Modulators (4)
  • New Bcl-2 Products
Catalog No. Product Name Information Product Use Citations Product Validations
E0011New 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.
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.
Nat Commun, 2022, 13(1):1199
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
Blood Cancer J, 2022, 12(3):39
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.
Signal Transduct Target Ther, 2022, 7(1):51
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
Cell Death Differ, 2022, 10.1038/s41418-022-00995-0
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
Biochem Biophys Res Commun, 2015, 463(4):870-5
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.
J Cell Mol Med, 2022, 10.1111/jcmm.17210
iScience, 2021, 24(9):103080
Platelets, 2020, 10.1080/09537104.2020.1724276
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.
J Biomol Struct Dyn, 2022, 1-11
Front Pharmacol, 2021, 12:632201
Molecules, 2021, 26(5)1210
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.
Clin Cancer Res, 2019, 10.1158/1078-0432.CCR-19-0775
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
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
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.
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.
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 Pharmacol, 2021, 12:632201
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.
Mol Med Rep, 2021, 23(1)40
J Biol Chem, 2015, 290(34):20841-55
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.
Haematologica, 2021, 10.3324/haematol.2021.278369
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Mol Cancer Ther, 2020, 19(10):2001-2011
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 Death Dis, 2022, 13(5):436
Cell Death Dis, 2021, 12(8):736
J Cell Sci, 2021, 134(24)jcs258966
S7800 A-1155463 A-1155463, 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).
J Immunother Cancer, 2022, 10(3)e004348
ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138
Pharmacol Res, 2022, 177:106095
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.
Nat Commun, 2022, 13(1):1199
Cell Death Dis, 2022, 13(5):436
ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138
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.
Cancer Cell, 2022, 40(3):301-317.e12
Cancer Cell, 2022, 40(2):168-184.e13
Nat Commun, 2022, 13(1):1199
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.
Platelets, 2020, 10.1080/09537104.2020.1724276
Am J Respir Crit Care Med, 2019, 200(1):84-97
PLoS Pathog, 2018, 14(6):e1007100
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.
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.
Signal Transduct Target Ther, 2022, 7(1):51
Nat Commun, 2022, 13(1):1606
Oncogene, 2022, 10.1038/s41388-022-02200-5
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.
Blood, 2022, blood.2021014011
Nat Commun, 2022, 13(1):1606
Cancer Res, 2022, canres.0218.2021
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.
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.
Signal Transduct Target Ther, 2022, 7(1):51
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.
Cell Death Dis, 2021, 12(5):495
Int J Mol Sci, 2021, 22(18)10107
S8836 S64315 (MIK665) S64315 (MIK665) 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.
Cell Death Dis, 2020, 8;11(6):443
Blood Adv, 2020, 4(5):819-829
Cancers (Basel), 2020, 12(8):E2182
S8865 BAI1 BAI1 is a direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM.
Cell Rep Methods, 2022, 2(3)100174
Cell Death Dis, 2021, 12(11):1050
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.
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.
Phytomedicine, 2022, 102:154182
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.
Cell Commun Signal, 2021, 19(1):115
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).
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.

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
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.
Mol Cancer Res, 2022, molcanres.0612.2021
Commun Biol, 2022, 5(1):39
Science, 2021, 371(6535)eabc5386
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.
Cell Death Dis, 2021, 12(11):1050
Life Sci, 2021, S0024-3205(21)01048-1
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.
E0124New 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
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.
Emerg Microbes Infect, 2022, 1-29
Cancer Res, 2021, canres.0955.2021
Front Cell Dev Biol, 2021, 9:765973
S6709New 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.

Emerg Microbes Infect, 2022, 1-29
Front Cell Dev Biol, 2021, 9:765973
S7100 WEHI-539 HCl WEHI-539 HCl (WEHI-539 hydrochloride) 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.
Cell Death Differ, 2021, 10.1038/s41418-021-00816-w
Commun Biol, 2021, 4(1):20
Mol Pharmacol, 2019, 96(4):419-429
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.
Cell Signal, 2022, S0898-6568(22)00041-9
Leukemia, 2019, 33(2):319-332
Molecules, 2018, 23(11)E3030
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).
S6895New TCPOBOP TCPOBOP is a constitutive androstane receptor (CAR) agonist. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
E2028New Humanin (human) 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.
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 Kaempferol-3-O-rutinoside Kaempferol-3-O-rutinoside (Nicotiflorin, Nikotoflorin, Kaempferol 3-O-β-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.
S8199 Ruxotemitide (LTX 315) Ruxotemitide (LTX 315, Oncopore) 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
E0011New 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.
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.
Nat Commun, 2022, 13(1):1199
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
Blood Cancer J, 2022, 12(3):39
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.
Signal Transduct Target Ther, 2022, 7(1):51
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
Cell Death Differ, 2022, 10.1038/s41418-022-00995-0
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
Biochem Biophys Res Commun, 2015, 463(4):870-5
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.
J Cell Mol Med, 2022, 10.1111/jcmm.17210
iScience, 2021, 24(9):103080
Platelets, 2020, 10.1080/09537104.2020.1724276
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.
J Biomol Struct Dyn, 2022, 1-11
Front Pharmacol, 2021, 12:632201
Molecules, 2021, 26(5)1210
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.
Clin Cancer Res, 2019, 10.1158/1078-0432.CCR-19-0775
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
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
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.
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.
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 Pharmacol, 2021, 12:632201
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.
Mol Med Rep, 2021, 23(1)40
J Biol Chem, 2015, 290(34):20841-55
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.
Haematologica, 2021, 10.3324/haematol.2021.278369
Cell Chem Biol, 2021, S2451-9456(21)00213-0
Mol Cancer Ther, 2020, 19(10):2001-2011
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 Death Dis, 2022, 13(5):436
Cell Death Dis, 2021, 12(8):736
J Cell Sci, 2021, 134(24)jcs258966
S7800 A-1155463 A-1155463, 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).
J Immunother Cancer, 2022, 10(3)e004348
ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138
Pharmacol Res, 2022, 177:106095
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.
Nat Commun, 2022, 13(1):1199
Cell Death Dis, 2022, 13(5):436
ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138
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.
Cancer Cell, 2022, 40(3):301-317.e12
Cancer Cell, 2022, 40(2):168-184.e13
Nat Commun, 2022, 13(1):1199
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.
Platelets, 2020, 10.1080/09537104.2020.1724276
Am J Respir Crit Care Med, 2019, 200(1):84-97
PLoS Pathog, 2018, 14(6):e1007100
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.
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.
Signal Transduct Target Ther, 2022, 7(1):51
Nat Commun, 2022, 13(1):1606
Oncogene, 2022, 10.1038/s41388-022-02200-5
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.
Blood, 2022, blood.2021014011
Nat Commun, 2022, 13(1):1606
Cancer Res, 2022, canres.0218.2021
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.
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.
Signal Transduct Target Ther, 2022, 7(1):51
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.
Cell Death Dis, 2021, 12(5):495
Int J Mol Sci, 2021, 22(18)10107
S8836 S64315 (MIK665) S64315 (MIK665) 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.
Cell Death Dis, 2020, 8;11(6):443
Blood Adv, 2020, 4(5):819-829
Cancers (Basel), 2020, 12(8):E2182
S8865 BAI1 BAI1 is a direct allosteric inhibitor of BAX with a dissociation constant (Kd) of 15.0 ± 4 μM.
Cell Rep Methods, 2022, 2(3)100174
Cell Death Dis, 2021, 12(11):1050
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.
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.
Phytomedicine, 2022, 102:154182
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.
Cell Commun Signal, 2021, 19(1):115
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).
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.

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
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.
Mol Cancer Res, 2022, molcanres.0612.2021
Commun Biol, 2022, 5(1):39
Science, 2021, 371(6535)eabc5386
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.
Cell Death Dis, 2021, 12(11):1050
Life Sci, 2021, S0024-3205(21)01048-1
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.
E0124New 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
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.
Emerg Microbes Infect, 2022, 1-29
Cancer Res, 2021, canres.0955.2021
Front Cell Dev Biol, 2021, 9:765973
S6709New 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.

Emerg Microbes Infect, 2022, 1-29
Front Cell Dev Biol, 2021, 9:765973
S7100 WEHI-539 HCl WEHI-539 HCl (WEHI-539 hydrochloride) 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.
Cell Death Differ, 2021, 10.1038/s41418-021-00816-w
Commun Biol, 2021, 4(1):20
Mol Pharmacol, 2019, 96(4):419-429
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.
Cell Signal, 2022, S0898-6568(22)00041-9
Leukemia, 2019, 33(2):319-332
Molecules, 2018, 23(11)E3030
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).
S6895New TCPOBOP TCPOBOP is a constitutive androstane receptor (CAR) agonist. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
E2028New Humanin (human) 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.
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 Kaempferol-3-O-rutinoside Kaempferol-3-O-rutinoside (Nicotiflorin, Nikotoflorin, Kaempferol 3-O-β-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.
S8199 Ruxotemitide (LTX 315) Ruxotemitide (LTX 315, Oncopore) 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
E0011New 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.
E0124New 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
S6709New 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.

Emerg Microbes Infect, 2022, 1-29
Front Cell Dev Biol, 2021, 9:765973
S6895New TCPOBOP TCPOBOP is a constitutive androstane receptor (CAR) agonist. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
E2028New Humanin (human) 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.
Tags: Bcl-2 apoptosis | Bcl-2 inhibition | Bcl-2 protein | Bax apoptosis | Bak protein | Bax protein | Bcl-2 cancer | Bcl-2 expression | Bcl-2 lymphoma | Bcl-2 protein family | Bak apoptosis | Bcl-2 pathway | Bcl-2 phosphorylation | Mcl-1 apoptosis | Bcl-xL apoptosis | Bcl-2 apoptosis pathway | Bcl-2 activation | Bcl-xL protein | Bcl-2 cleavage | Bcl-2 inhibitor clinical trial | Bcl-2 inhibitor review