quizartinib and imidazo(1-2-a)pyridine

FMS-like tyrosine kinase 3 (FLT3) with an internal tandem duplication (ITD) mutation has been validated as a driver lesion and a therapeutic target for acute myeloid leukemia (AML). Currently, several potent small-molecule FLT3 kinase inhibitors are being evaluated or have completed evaluation in clinical trials. However, many of these inhibitors are challenged by the secondary mutations on kinase domain, especially the point mutations at the activation loop (D835) and gatekeeper residue (F691). To overcome the resistance challenge, we identified a novel series of imidazo[1,2-a]pyridine-thiophene derivatives from a NIMA-related kinase 2 (NEK2) kinase inhibitor CMP3a, which retained inhibitory activities on FTL3-ITD

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Molecular Structure; Mutation; NIMA-Related Kinases; Protein Kinase Inhibitors; Pyridines; Structure-Activity Relationship; Thiophenes