compound 49

Compound 49 is a novel small molecule inhibitor belonging to the furo[2,3-d]pyrimidin-1,3,4-thiadiazole-urea series, specifically developed to target the FMS-like tyrosine kinase 3 (FLT3) receptor. It is particularly effective against the internal tandem duplication (ITD) mutation and the F691L gatekeeper mutation, which are significant drivers of resistance in acute myeloid leukemia (AML). Mechanistically, compound 49 acts as a type II kinase inhibitor, binding to the active site of FLT3 and inhibiting its phosphorylation, which subsequently suppresses downstream signaling through STAT5 and ERK1/2. In preclinical evaluations, it demonstrated nanomolar potency against FLT3-ITD-expressing AML cell lines (MOLM-13 and MV4-11) and showed superior efficacy compared to established inhibitors like sorafenib and quizartinib in Ba/F3 mutant models.

Other names

furo[2,3-d]pyrimidin-4-ylsulfanyl-1,3,4-thiadiazole derivative 49