Document Report Card
Basic Information
ID: ALA5236627
Journal: Bioorg Med Chem Lett
Title: Synthesis and biological activity evaluation of novel 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines.
Authors: Vlková K, Padrtová R, Gucký T, Peřina M, Řezníčková E, Kryštof V.
Abstract: Mutation of FLT3 protein kinase is often associated with deregulated cell proliferation in acute myeloid leukemia and the inhibition of this kinase is a potential therapeutic strategy. We report a novel series of 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines prepared in an effort to study their biological activity particularly toward FLT3-ITD and its downstream regulators as well as toward CDK2 and CDK9. Derivative 10b was capable to strongly inhibit all kinases and its selectivity in FLT3-ITD expressing cell lines MOLM13 and MV4-11 was in line with FLT3-ITD inhibition. Further biochemical analyses and molecular docking confirmed FLT3 as a cellular target of 10b.
CiteXplore: 36496201