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.

AT-101 is orally bioavailable solvate of R-(-)-enantiomer of gossypol with potential antineoplastic activity. As a BH3 mimetic, AT-101 binds to the hydrophobic surface binding groove BH3 of the anti-apoptotic proteins Bcl-2 and Bcl-xL, blocking their heterodimerization with pro-apoptotic members of the Bcl-2 family of proteins such as Bad, Bid, and Bim; this may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. AT-101 induces apoptosis in vitro through activation of caspase-9; cytotoxic to multiple myeloma and drug-resistant cell lines. AT-101 delays onset of androgen-independent growth of VCaP prostate cancer xenografts in vivo.

ABT-199

ABT-737

BAM7

HA14-1

MIM1

TW-37

WEHI-539