Bcl-2 Antagonist

Gossypol binds to Bcl-xL protein and Bcl-2 protein with K_is of 0.5-0.6 μM and 0.2-0.3 mM, respectively.

BDA-366 is a potent Bcl2 antagonist (K_i = 3.3 nM), binding Bcl2-BH4 domain with high affinity and selectivity. BDA-366 induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer cells.

YC137 is a potent Bcl-2 antagonist with K_is of 1.3 μM and >100 μM for Bcl-2 and Bcl-xL when assayed in Bis-Tris buffer, respectively. YC137 inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an interaction essential for the antiapoptotic activity of Bcl-2. YC137 selectively induces apoptosis of Bcl-2-dependent cells. YC137 has the potential for breast cancer research.

A-371191 is a selective Bcl-XL antagonist with a K_i <0.5 μM, and also acts as a mitochondria-targeting agent and chemosensitizer. A-371191 restores the sensitivity of cancer cells overexpressing Bcl-XL to Cisplatin (HY-17394) and Doxorubicin (HY-15142A). A-371191 reduces tumor volume in mice with intraperitoneal tumors. A-371191 can be used in the research of acute myeloid leukemia.