Cancer

In vitro and cell culture studies suggest stapled peptide inhibitors of MCL1 could help treat ALL and MM. Modification of previously identified peptide-based inhibitors of MCL1 with hydrocarbon cross-links to stabilize α-helices and in vitro activity assays yielded two stapled peptides that bound MCL1 with IC₅₀ values of 25 and 80 nM. In MCL1-dependent ALL and MM cell lines, the stapled peptides increased apoptosis compared with a tool compound BCL-2/Bcl-XL inhibitor. Next steps include testing the stapled peptides targeting MCL1 in mouse models of undisclosed MCL-1-dependent cancers.

Amgen Inc. has AMG 176, an MCL1 inhibitor, in Phase I testing to treat relapsed or refractory MM...