Venetoclax (ABT-199; GDC-0199) is a highly selective, orally bioavailable small-molecule inhibitor of Bcl-2, exhibiting sub-nanomolar binding affinity with a Ki of less than 0.01 nM. This compound has been demonstrated to induce autophagy, highlighting its role in modulating programmed cell death pathways. In vitro studies reveal that Venetoclax exhibits potent cytotoxic activity against FL5.12-BCL-2 cells, with an EC50 of 4 nM, while showing markedly reduced efficacy against FL5.12-BCL-XL cells (EC50 = 261 nM), underscoring its selectivity for Bcl-2 over Bcl-XL. The selectivity of Venetoclax is further corroborated in cellular mammalian two-hybrid assays, where it effectively disrupts BCL-2-BIM protein-protein interactions with an EC50 of 3 nM. In contrast, it demonstrates significantly weaker activity against BCL-XL-BCL-XS and MCL-1-NOXA complexes, with EC50 values of 2.2 μM, reinforcing its specificity for Bcl-2-dependent apoptotic regulation. In vivo efficacy studies utilizing xenograft models derived from RS4;11 cells, a representative model of acute lymphoblastic leukemia (ALL), demonstrate that a single oral dose of Venetoclax (12.5 mg/kg) achieves a maximal tumor growth inhibition (TGImax) of 47% (P < 0.001) and a tumor growth delay (TGD) of 26% (P < 0.05). These results indicate robust anti-tumor activity in a Bcl-2-dependent malignancy.

ZH97 is a selective and covalent small-molecule inhibitor of BFL-1 protein with binding Ki of 0.41 uM, >200-fold selectivity over MCL-1.ZH97 does not bind to BCL-xL, BCL-2, TEAD2, TEAD4, MDM2, MDMX, BRD2 BD1, BRD2 BD2, BRD3 BD1, BRD3 BD2, BCL9, PD1/PD-L1 (Ki>400 uM).ZH97 modifies BFL-1 at the C55 residue, blocks BFL-1/BID interaction in vitro.ZH97 dose-dependently increased cytoplasmic cytochrome c level in U937 cells, has cell growth inhibition with IC50 of 2.8 uM, 5.5 uM, 7.7 uM, 6.8 uM, and 3.9 uM in U937, Kasumi-1, K562, MM.1S, and MV4-11 cell lines, respectively.ZH97 inhibits BFL-1/PUMA interaction in cell lysate and is effective in cancer cells that harboring highexpression level of BFL-1.

ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤ 1 nM, respectively.

A-1155463 is a highly potent and selective BCL-XL inhibitor.

Lacutoclax is a Bcl-2 inhibitor with antineoplastic activity.

WK500B is an orally available small molecule BCL6 inhibitor with IC50 of 1.39 uM (HTFR), exhibits potent efficacy against DLBCL in vitro and in vivo.

WK499 (WK-499) is a small molecule inhibitor of BCL6 with IC50 of 11.7 nM in HTRF assay, directly binds to BCL6 BTB (SPR KD=148 nM), inhibits the BCL6-mediated transcriptional repression activity.

WK369 (WK-369) is a specific small molecule inhibitor of BCL6, directly binds to the BCL6-BTB domain (SPR KD=2.24 uM) and blocks the interaction between BCL6 and SMRT with IC50 of 0.32 uM in HTRF assays.

Sonrotoclax (BGB-11417) is a potent, selective and second-generation BCL2 inhibitor with IC50 of 0.014 nM and SPR KD value of 0.046 nM, overcomes BCL2 G101V mutation-induced venetoclax resistance.

OICR12694 (OICR 12694, JNJ-65234637) is a potent, selective, and orally bioavailable BCL6-BTB inhibitor with SPR KD value of 5 nM.

A potent inhibitor of Bcl-2 family with IC50s of 1-7 uM for Bcl-2, Bcl-XL, Bcl-w, Bcl-B, Mcl-1 and Bfl-1.

MI-238 (MI 238) is a potent and specific Mcl-1 inhibitor with Ki of 0.45 uM to human Mcl-1 protein in FP assays, disrupts the association of Mcl-1 with BH3-only proteins.

M109S is a small molecule protecting cells from mitochondria-dependent apoptosis wtih EC50 of 23.4 nM in iBax cells, directly interacts with Bax (Kd=153 nM, MST assay) and inhibits Bax activation.

GSK137 is a potent, small-molecule BCL6 inhibitor binding to BCL6 BTB-POZ domain, displaces peptides derived from the human SMRT co-repressor from the BCL6 BTB-POZ domain in a TR-FRET assay with a pIC50 of 8.0.

DC-B01 is a novel small molecule BCL-2 inhibitor that binds to the BH4 domain with KD of 2.16 uM, disrupts the BCL-2/c-Myc interaction and consequently suppresses the transcriptional activity of c-Myc.

CGDF-190-20 is a selective small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 365 nM in FP assays.

CGDF-183-20 is a selective small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 264 nM in FP assays.

CCT374705 is a potent, selective, in-vivo active BCL6 inhibitor with TR-FRET IC50 of 6 nM.

CCT372064 is a potent, ligand-efficient inhibitor of BCL6 with IC50 of 3.9 nM and 12 nM in TR-FRET and cellular NanoBRET assays, respectively.

BI-5273 is a negative control compound of BI-3802 and BI-3812, which are potent and efficacious BCL6 degrader and inhibitor, respectively.

BDM53787 is a selective small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 0.8 uM (inhibition FITC–Bim BH3 binding to Bfl-1).

BDM49234 is a selective small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 6.3 uM (inhibition FITC–Bim BH3 binding to Bfl-1).

BDM44931 is a small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 1.3 uM.

BDM44898 is a small molecule inhibitor of anti-apoptotic protein BCL2A1/Bfl-1 with IC50 of 1.6 uM.

BAU-243 (BAU243) is a novel BH3 mimetic Bcl-2 inhibitor with a high affinity, effectively reduces overall GBM cell proliferation including a subpopulation of cancer-initiating cells.

BXI-72 (NSC334072) is a potent, selective small molecule Bcl-XL inhibitor that targets the BH3 domain of Bcl-XL (Kd=0.9 nM).

Bim-IN-1 is a potent Bim expression inhibitor. Bim-IN-1 reduces Bim expression levels and has little inhibitory effect upon protein kinase A activity and minimal toxicity.

BFL-1 inhibitor 4E14 (4E14) is a potent, selective, covalent BFL-1 inhibitor that disrupt BH3-binding activity with IC50 of 1.3 uM, targets a unique C55 residue in the BFL-1 groove.4E14 blocks BFL-1 suppression of BAX-mediated mitochondrial apoptosis.

UMI-77 is a selective Mcl-1 inhibitor with Ki of 490 nM, showing selectivity over other members of Bcl-2 family.

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, respectively.