ABT-263

ABT-263, a novel, orally bioavailable, BH3 mimetic, binds with high affinity (Ki ≤ 1nM) and inhibits multiple antiapoptotic Bcl-2 family proteins. ABT-263 displays activity (EC50 ≤ 1µM) against human lymphoid and small cell lung cancer cell lines. Mechanism based preclinical toxicities include reductions in circulating lymphocytes, apoptosis of circulating platelets, and decreased spermatogenesis, mediated by inhibition of Bcl-2, Bcl-XL and Bcl-w with IC50 values of ≤ 1 nM, ≤0.5 nM and ≤ 1 nM, respectively.