Bcl-2 Family

Bcl-2 homology domain-3 (BH3) mimetic,antagonize all antiapoptotic Bcl-2 family proteins (average IC50, 3 umol/L), including Mcl-1 (IC50, 2.9 umol/L) and Bfl-1 (IC50, 5 umol/L).

ABT-199 is a so-called BH3-mimetic drug, which is designed to block the function of the protein Bcl 2.

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.

Gambogic acid is a natural product isolated from the Garcinia hanburyi tree. Gambogic Acid 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.

ABT-737 is a pan-Bcl-2 inhibitor. IC50 values ranged from 192 nM (the pre-B cell line Hal-01) to <10 μM (Nalm-6, K562 and HL-60).

AVN-944 (also known as VX-944) serves as an effective oral inhibitor, specifically targeting and inhibiting IMPDH (inosine monophosphate dehydrogenase). This enzyme plays a crucial role as a rate-limiting factor in the synthesis of guanine nucleotides from scratch. Additionally, AVN-944 acts against the synthesis of RNA in arenaviruses, effectively preventing arenavirus infections. Demonstrating a wide spectrum of anti-cancer properties, AVN-944 is utilized in research related to multiple myeloma (MM) and acute myeloid leukemia (AML).

Bax channel blocker is a potent inhibitor of Bax-mediated mitochondrial cytochrome C release (IC50 = 0.52 μM).

BAM 7 binds the BAX trigger site with an EC50 ~ 3.3 μM as measured in a competitive FP assay using FITC-BIM SAHB and BAX.

Bcl-2 Inhibitor contains a mixture of two tautomers. A potent, cell-permeable, Bcl-2 inhibitor competes with Bak BH3 peptide for binding to Bcl-2 and Bcl-XL in vitro (IC50 =10 uM and 7 uM, respectively).

A-1210477 is a potent and selective MCL-1 inhibitor. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines.

A-1155463 is a highly potent and selective BCL-XL inhibitor, A-1155463 shows picomolar binding affinity to BCL-XL (Ki = <0.01 nM), and >1000-fold weaker binding to BCL-2 (Ki = 80 nM) and related proteins BCL-W (Ki = 19 nM) and MCL-1 (Ki > 440 nM)

MIM1 is a selective small molecule inhibitor of Mcl-1(IC50= 4.8 μM) that overcomes Mcl-1-dependent leukemia cell survival.

TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1.

BM-1244 is a selective inhibitor of Bcl-xL and Bcl-2, exhibiting Ki values of 134 nM and 450 nM, respectively. This compound induces apoptosis and suppresses tumor growth through the release of cytochrome C and Smac from mitochondria, leading to caspase-3 activation and PARP cleavage. BM-1244 has demonstrated synergistic effects with chemotherapy in vivo, making it a valuable research tool for studying colorectal cancer, acute myeloid leukemia, and gastric cancer.

Pelcitoclax is a potent inhibitor of Bcl-2 and Bcl-xl, designed to induce apoptosis in cancer cells. Its primary mechanism involves disrupting the anti-apoptotic activity of these proteins, leading to increased cell death in malignant tissues. Pelcitoclax is utilized in research to explore therapeutic strategies against various malignancies and to study apoptotic pathways in cellular models.

Lisaftoclax is a potent inhibitor of the anti-apoptotic proteins Bcl-2 and Bcl-xl. With IC50 values of 2 nM for Bcl-2 and 5.9 nM for Bcl-xl, Lisaftoclax demonstrates significant anti-tumor activity. This compound is primarily utilized in research focused on cancer therapy, particularly in studies exploring mechanisms of apoptosis and the role of Bcl-2 family proteins in tumor survival.

AS1411 (AGRO-100) is a G-rich oligonucleotide aptamer that selectively targets nucleolin, a nucleoprotein overexpressed on the surface and within the nucleus of many cancer cells. It inhibits tumor cell proliferation by disrupting nucleolin-containing complexes, thereby affecting key oncogenic processes. AS1411 has been shown to reduce PRMT5 expression and inhibit tumor growth in DU145 prostate cancer cells, and to block the interaction between nucleolin and *bcl-2* mRNA in MCF-7 breast cancer cells, leading to decreased Bcl-2 protein levels and enhanced apoptosis. Beyond its intrinsic anticancer activity, AS1411 serves as a precision-targeting carrier for the delivery of nanoparticles, oligonucleotides, and small molecules to cancer cells. AS1411-conjugated gold nanospheres have demonstrated effective inhibition of breast cancer cell proliferation in vitro and in vivo, with the added advantage of crossing the blood-brain barrier and exhibiting low tissue toxicity, making AS1411 a versatile platform for targeted cancer therapy and drug delivery.

BM-1074 is a potent and efficacious Bcl-2/Bcl-xL inhibitor with Ki of <1 nM.

WEHI539 is a selective inhibitor of Bcl-XL with IC50 of 1.1 nM.

WEHI-539 hydrochloride is a small-molecule inhibitor of BCL-xL with IC50 value of 1.1 nM.

HA14-1 interacts with Bcl-2 and inhibits the antiapoptotic effect of Bcl-2.

Jaceosidin is a pharmacologically active flavone derived from Artemisia argyi, inhibits phorbol-ester-induced upregulation of COX-2 and MMP-9 by blocking phosphorylation of ERK-1 and -2 in cultured human mammary epithelial cells.

AT101, 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; does not inhibit BIR3 domain and BID

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

A-385358 is an inhibitor of Bcl-XL that enhances the in vitro cytotoxic activity of numerous chemotherapeutic agents (paclitaxel, etoposide, cisplatin, and doxorubicin) in several tumor cell lines.

FX1 is an inhibitor of the transcription factor B cell lymphoma 6 (BCL6) with IC50 value of ~35 μM.

AZD-4320 is a BH3 mimetic and dual Bcl-2/Bcl-XL inhibitor.

Marinopyrrole A, aslo known as Maritoclax, is a selective inhibitor of Mcl-1 with IC50 value of 10.1μM.

BT2 is a BCKDC kinase (BDK) inhibitor with an IC50 of 3.19 μM.

S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a Kd of 0.19 nM for human MCL1.

(R)-MIK665 is the less active enantiomer of MIK665. MIK665 is a special Mcl-1 inhibitor with an IC50 of 1.81 nM.

AMG-176 is a potent, selective and orally bioavailable MCL-1 inhibitor, with a Ki of 0.13 nM.

S55746 (BLC201) is a potent, orally active and selective BCL-2 inhibitor, with a Ki of 1.3 nM and a Kd of 3.9 nM. S55746 (BLC201) has antitumor activity with low toxicity.

MIK665 (S-64315) is a special Mcl-1 inhibitor extracted from patent WO2016207225A1, compound Preparation 13, has an IC50 of 1.81 nM.

VU661013 is a MCL-1 Inhibitor Combined with Venetoclax Rescues Venetoclax Resistant Acute Myelogenous Leukemia.

ML311 is a potent and selective inhibitor of the Mcl-1/Bim interaction

Thevetiaflavone could upregulate the expression of Bcl?2 and downregulate that of Bax and caspase?3.

Mcl1-IN-2 is a selective Mcl-1 inhibitor.

Mcl1-IN-1 is a potent and selective inhibitor of the apoptosis regulating proteins Mcl-1.

Mcl1-IN-8 (Comp8) is a Mcl-1-PUMA interface inhibitor, with a Ki of 0.3 μM. Mcl1-IN-8 (Comp8) exhibits dual activity on reduce PUMA-dependent apoptosis while deactivating Mcl-1-mediated anti-apoptosis in cancer cells.

Mcl1-IN-9 is a potent myeloid cell leukemia-1 (Mcl-1) Inhibitor with an IC50 of 446 nM in reengineered BCR-ABL+ B-ALL cells and a Ki of 0.03 nM.

PROTAC Mcl1 degrader-1 (compound C3), a proteolysis targeting chimera (PROTAC), is a potently and selectively Mcl-1 inhibitor with an IC50 of 0.78 μM.

NPB is a specific and potent inhibitor of BAD phosphorylation at Ser99, with an IC50 of 0.41 μM.

Mcl-1 antagonist 1 is a Mcl-1 protein antagonist extracted from patent WO2019173181, compound 200.

TCPOBOP is an agonist of the constitutive androstane receptor (CAR) (EC50 = 20 nM). TCPOBOP enhances the nuclear receptor CAR transactivation of cytochrome P450 (CYP), as dose-dependent direct agonist of CAR.

Mcl1-IN-11 (Compound G) is a selective Mcl-1 inhibitor, less potent at Bcl-2, with Kis of 0.06 and 4.2 μM, respectively.

dMCL1-2 is a potent and selective degrader of myeloid cell leukemia 1 (MCL1) based on PROTAC, which binds to MCL1 with a KD of 30 nM. dMCL1-2 activats the cellular apoptosis machinery by degradation of MCL1.

Mcl1-IN-12 (Compound F) is a selective Mcl-1 inhibitor, less potent at Bcl-2, with Kis of 0.29 and 3.1 μM, respectively. Anti-tumor activity.

MCL-1/BCL-2-IN-4 (Compound 7) is a potent and selective Mcl-1 and Bcl-2 dual inhibitor.