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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1985-2009
Number of pages	25
Journal	ACS Omega
Volume	2
Issue number	5
DOIs	https://doi.org/10.1021/acsomega.7b00144
State	Published - May 31 2017
Externally published	Yes

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Publisher Copyright:
© 2017 American Chemical Society.

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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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doi = "10.1021/acsomega.7b00144",

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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

Y1 - 2017/5/31

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/85028978080

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

U2 - 10.1021/acsomega.7b00144

DO - 10.1021/acsomega.7b00144

M3 - Article

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SN - 2470-1343

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

Abstract

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