Bcl-2/Bcl-xl inhibitor 1

Navitoclax (ABT-263) is a potent oral Bcl-2 inhibitor that binds to Bcl-xL, Bcl-2, and Bcl-w proteins (Ki<1 nM), demonstrating antitumor activity and inducing apoptosis.

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).

Desmorpholinyl Navitoclax-NH-Me (Desmorpholinyl ABT-263-NH-Me) is a Bcl-xL inhibitor, which can be employed alongside a CRBN ligand to synthesize XZ739, a PROTAC BCL-XL degrader [1] [2].

CAY10404 (3-(4-METHYLSULPHONYLPHENYL)-4-PHENYL-5-T) is a potent and highly selective inhibitor of COX-2 and COX-1. It is also a potent inhibitor of PKB Akt and MAPK signalling pathways and induces apoptosis in NSC-LC cells, with analgesic, anti-inflammatory and anti-cancer activities.

Lisaftoclax (Bcl-2 Bcl-xl inhibitor 1) is an oral dual inhibitor of Bcl-2 and Bcl-xl, with IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively. Lisaftoclax is used to treat chronic lymphocytic leukemia (CLL) by inhibiting the action of the BCL-2 protein, which promotes the death of leukemia cells.

BM 957 is an effective Bcl-2 and Bcl-xL inhibitor (Kis: 1.2 and <1 nM; IC50s: 5.4 and 6.0 nM).

BH3I-1 (BHI1) is a Bcl-2 antagonist.

MLS-0053105, a chloromaleimide, functions as a selective inhibitor of BFL-1, exhibiting an IC50 of 0.4 µM against Bfl-1 F-Bid. Its inhibitory potency is over tenfold lower for Bcl-W, Bcl-2, and Bcl-XL, and it shows no activity against Bcl-B and Mcl-1.

BM-962 (Compound 31) is a potent small-molecule inhibitor with an IC50 value of 4 nM (Ki=0.8 nM) for Bcl-2 and an IC50 of 3.9 nM (Ki<1 nM) for Bcl-xL. It inhibits H1417 and H146 cell lines with IC50 values of 9 and 13 nM, respectively, and shows potential for use in cancer research.

Apogossypolone (ApoG2) is a semi-synthesized derivative of gossypol which is a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins with K i values of 35, 25 and 660 nM for Bcl-2, Mcl-1 and Bcl-X L, respectively. Apogossypolone shows antitumor activities, induces cell apoptosis [1] and autophagy [2]. Apogossypolone also has antifungal activity [3].

BM-1074 is a potent and highly efficacious inhibitor of Bcl-2 Bcl-xL, with a Ki value of < 1nM [1].

BM-1244 is a potent Bcl-xL/Bcl-2 inhibitor with Kis of 134 and 450 nM for Bcl- xL and Bcl-2, respectively. BM-1244 inhibits senescent fibroblasts (SnCs) with an EC50 of 5 nM[1].

S65487 (VOB560) is a potent and selective Bcl-2 inhibitor. S65487 is also active on BCL-2 mutations, such as G101V and D103Y. S65487 has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 induces apoptosis and has anticaner activities[1][2].

Pelcitoclax (APG-1252) is a potent inhibitor of Bcl-2 and Bcl-xl proteins, demonstrating substantial antineoplastic and pro-apoptotic activities[1].

S65487 (VOB560) hydrochloride, a potent and selective Bcl-2 inhibitor, is effective against BCL-2 mutations, including G101V and D103Y, while exhibiting poor affinity for MCL-1, BFL-1, and BCL-XL. This compound induces apoptosis and possesses anticancer activities.

S65487 (VOB560) sulfate, a potent and selective Bcl-2 inhibitor, demonstrates activity against BCL-2 mutations, including G101V and D103Y, while showing poor affinity for MCL-1, BFL-1, and BCL-XL. It induces apoptosis and possesses anticancer activities.

Mcl-1 inhibitor 6 is a potent, orally active chemical compound that selectively inhibits the myeloid cell leukemia 1 (Mcl-1) protein, with a high affinity (K d = 0.23 nM) and binding activity (K i = 0.02 μM). This compound exhibits exceptional selectivity over other members of the Bcl-2 family, including Bcl-2, Bcl2A1, Bcl-xL, and Bcl-w (K d >10 μM). Notably, Mcl-1 inhibitor 6 demonstrates strong antitumor activity.

TW-37 is an nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 (Ki: 0.29 1.11 0.26 μM).

Sabutoclax (BI-97C1)(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.

A-1331852 is a potent and selectiveBCL-XL inhibitor and may be useful in the treatment of cancer, immune and autoimmune diseases.

Bcl-2-IN-11 (compound 6) is a potent and selective Bcl-2 activity inhibitor with an IC50 of 0.9 nM and minimal inhibition against Bcl-xl (IC50 > 1000 nM). It is used in cancer research related to Bcl-2 family protein overexpression, particularly in hematologic malignancies like acute lymphoid leukemia, while minimizing the risk of side effects such as thrombocytopenia [1] by sparing Bcl-xl.

NWP-0476 is a modified BCL-2 BCL-xL inhibitor with enhanced specificity for BCL-xL, suitable for research on relapsed T-acute lymphoblastic leukemia (T-ALL) [1].

(S)-Sabutoclax ((S)-BI-97C1), an optically pure derivative of apogossypol, serves as a pan-active inhibitor of the antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. It effectively blocks the binding of BH3 peptides to key proteins in the family, including Bcl-XL, Bcl-2, Mcl-1, and Bfl-1, displaying inhibitory concentration (IC50) values of 0.31, 0.32, 0.20, and 0.62 μM, respectively. Furthermore, (S)-Sabutoclax demonstrates potent efficacy in inhibiting the growth of various cancer cell lines, such as those from human prostate cancer, lung cancer, and lymphoma, with half-maximal effective concentration (EC50) values of 0.13, 0.56, and 0.049 μM, respectively. This compound is utilized in research focusing on apoptosis-based cancer therapies [1].

BDM19 binds to and activates cytosolic BAX dimers, inducing cell apoptosis alone or when used in combination with the BCL-2 BCL-XL inhibitor, Navitoclax [1].