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

9 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
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

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2017 American Chemical Society.

ASJC Scopus subject areas

Chemistry (all)
Chemical Engineering (all)

Access to Document

10.1021/acsomega.7b00144

Cite this

@article{1da4d7f9e0fe4a2796034e5354818108,

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.",

author = "Jarusiewicz, {Jamie A.} and Jeon, {Jae Yoon} and Connelly, {Michele C.} and Yizhe Chen and Lei Yang and Baker, {Sharyn D.} and Guy, {R. Kiplin}",

note = "Funding Information: This work was supported by the Department of Defense (CA093469P2), NCI (CA138744-07), St. Jude Children{\textquoteright}s Research Hospital, and the American Lebanese Syrian Associated Charities (ALSAC). Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

month = may,

day = "31",

doi = "10.1021/acsomega.7b00144",

language = "English",

volume = "2",

pages = "1985--2009",

number = "5",

}

TY - JOUR

T1 - Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

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

N1 - Funding Information: 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). Publisher Copyright: © 2017 American Chemical Society.

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 - http://www.scopus.com/inward/record.url?scp=85028978080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028978080&partnerID=8YFLogxK

U2 - 10.1021/acsomega.7b00144

DO - 10.1021/acsomega.7b00144

M3 - Article

AN - SCOPUS:85028978080

VL - 2

SP - 1985

EP - 2009

IS - 5

ER -

Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this