Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity
ZF Tao, L Hasvold, L Wang, X Wang… - ACS medicinal …, 2014 - ACS Publications
ZF Tao, L Hasvold, L Wang, X Wang, AM Petros, CH Park, ER Boghaert, ND Catron, J Chen…
ACS medicinal chemistry letters, 2014•ACS PublicationsA-1155463, a highly potent and selective BCL-XL inhibitor, was discovered through nuclear
magnetic resonance (NMR) fragment screening and structure-based design. This compound
is substantially more potent against BCL-XL-dependent cell lines relative to our recently
reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical
liabilities. 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 …
magnetic resonance (NMR) fragment screening and structure-based design. This compound
is substantially more potent against BCL-XL-dependent cell lines relative to our recently
reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical
liabilities. 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 …
A-1155463, a highly potent and selective BCL-XL inhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical liabilities. 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. A-1155463 thus represents an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization.
ACS Publications