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Article

Discovery of FLC-8 as the First Covalent FLT3 Inhibitor Targeting Cys807 for FLT3 Mutant Acute Myeloid Leukemia.

Journal of medicinal chemistry - 23 Apr 2026

Wang Zi-Xuan, Jing Xiao-Long, Liu Qian, Xian Tong, Yang Jin, Zhang Meng-Yuan, Li Qing-Qing, Cai Jiao, Yu Yan-Cheng, Sun Shan-Liang, Li Nian-Guang, Shi Zhi-Hao

Abstract excerpt

FLT3 is a validated therapeutic target in acute myeloid leukemia (AML), yet resistance mutations frequently limit current inhibitors. Here, we report a series of 6-methylisoxazolo[5,4-b]pyridin-3-amines that covalently target Cys807, a previously unexploited nucleophilic residue within the FLT3 kinase domain. Compound 18 (FLC-8) potently inhibited FLT3-WT (IC50 = 10.2 nM) and clinically relevant mutants G697R...

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Identifiers

PMID: 41931375
DOI: 10.1021/acs.jmedchem.6c00511

Genes

FLT3

Variants

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

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