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Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.

ABSTRACT: Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure-activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.

SUBMITTER: Jarusiewicz JA

PROVIDER: S-EPMC5452050 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.

Jarusiewicz Jamie A JA Jeon Jae Yoon JY Connelly Michele C MC Chen Yizhe Y Yang Lei L Baker Sharyn D SD Guy R Kiplin RK

ACS omega 20170510 5

Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure-activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonst ...[more]

PMID: 28580438

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| S-EPMC5613053 | biostudies-literature

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