Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

Jamie A. Jarusiewicz; Jae Yoon Jeon; Michele C. Connelly; Yizhe Chen; Lei Yang; Sharyn D. Baker; R. Kiplin Guy

doi:10.1021/acsomega.7b00144

Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

Jamie A. Jarusiewicz
, Jae Yoon Jeon
, Michele C. Connelly
, Yizhe Chen
, Lei Yang
, Sharyn D. Baker
, R. Kiplin Guy

Pharmaceutical Sciences

Producción científica: Article › revisión exhaustiva

12 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	1985-2009
Número de páginas	25
Publicación	ACS Omega
Volumen	2
N.º	5
DOI	https://doi.org/10.1021/acsomega.7b00144
Estado	Published - may 31 2017

Nota bibliográfica

Publisher Copyright:
© 2017 American Chemical Society.

Financiación

This work was supported by the Department of Defense (CA093469P2), NCI (CA138744-07), St. Jude Children’s Research Hospital, and the American Lebanese Syrian Associated Charities (ALSAC).

Financiadores	Número del financiador
U.S. Department of Defense	CA093469P2
National Childhood Cancer Registry – National Cancer Institute	CA138744-07
St. Jude Children's Research Hospital
American Lebanese Syrian Associated Charities

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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title = "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.",

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AU - Jarusiewicz, Jamie A.

AU - Jeon, Jae Yoon

AU - Connelly, Michele C.

AU - Chen, Yizhe

AU - Yang, Lei

AU - Baker, Sharyn D.

AU - Guy, R. Kiplin

PY - 2017/5/31

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AB - 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.

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UR - https://www.scopus.com/pages/publications/85028978080#tab=citedBy

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VL - 2

SP - 1985

EP - 2009

JO - ACS Omega

JF - ACS Omega

IS - 5

ER -

Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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