Cancer
In vitro, cell culture, mouse and rat studies identified an inhibitor of internal tandem duplication (ITD)-mutant FLT3 that could help treat AML. Chemical synthesis and cell-based binding assays of analogs of two inhibitors of FLT3 and other receptor tyrosine kinases -- Nexavar sorafenib and a tool compound inhibitor -- yielded a phenylacetamide-based compound that inhibited proliferation of mouse pro B cells expressing ITD-mutant FLT3 with an IC50 of 32 nM. In mouse pro B cells expressing four other ITD mutations in FLT3, the compound inhibited proliferation with IC50 values of 32-85 nM. In three human AML cell lines expressing ITD-mutant FLT3, the compound inhibited growth with IC50 values of 284-466 nM. In a xenograft mouse model of AML expressing ITD-mutant FLT3, the compound decreased tumor growth compared with vehicle. In rats, the compound had a plasma half-life of 1.3 hours. Next steps could include optimization and testing of the compound in models of AML expressing ITD-mutant FLT3.
Amgen Inc. and Bayer AG market Nexavar for liver, renal and thyroid cancers and have the product in Phase III testing as an adjuvant for liver cancer...
BCIQ Target Profiles