BioCentury
ARTICLE | Distillery Therapeutics

Cancer

November 30, 2016 2:16 PM UTC

In vitro and mouse studies identified an MCL1 inhibitor that could help treat AML, lymphoma and MM. NMR-based fragment screening, chemical synthesis and optimization, and in vitro testing yielded a pyrimidinylthienofluorofuran-based propanoic acid analog that bound human MCL1 with a Kd of 0.19 nM. In xenograft mouse models of AML and MM, the compound decreased tumor growth compared with vehicle. In a mouse model of lymphoma, the compound increased survival. Next steps by Servier and Vernalis plc, in partnership with Novartis AG, include IND-enabling studies of analogs of the compound.

Ascenta Therapeutics Inc. and Ascentage Pharma Group Corp. Ltd. have AT-101, an MCL1 and B cell lymphoma 2 (BCL-2; BCL2) inhibitor, in Phase II testing for brain cancer and chronic lymphocytic leukemia (CLL). ...