A-1155463

A-1155463 is a highly potent and selective BCL-XL inhibitor (Ki=10 pM) ; shows >1000-fold weaker binding to BCL-2, BCL-W (Ki =19 nM) and MCL-1 (Ki >440 nM) ; inhibits H146 SCLC xenograft tumor growth in vivo. (In Vitro) :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) . A-1155463 demonstrates strong growth inhibition of over half of the colorectal cell lines as defined by EC50 values ≤0.5 μM in the presence of 10 % FBS. (In Vivo) :A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses.