Identification of New FLT3 Inhibitors That Potently Inhibit AML Cell Lines via an Azo Click-It/Staple-It Approach

Xiaochu Ma; Jie Zhou; Changhao Wang; Brandon Carter-Cooper; Fan Yang; Elizabeth Larocque; Jonathan Fine; Genichiro Tsuji; Gaurav Chopra; Rena G Lapidus; Herman O Sintim

doi:10.1021/acsmedchemlett.6b00468

Identification of New FLT3 Inhibitors That Potently Inhibit AML Cell Lines via an Azo Click-It/Staple-It Approach

ACS Med Chem Lett. 2017 Apr 14;8(5):492-497. doi: 10.1021/acsmedchemlett.6b00468. eCollection 2017 May 11.

Authors

Xiaochu Ma^{1

2

1}, Jie Zhou^{1

1}, Changhao Wang², Brandon Carter-Cooper³, Fan Yang², Elizabeth Larocque^{1

1}, Jonathan Fine^{1

1}, Genichiro Tsuji^{1

1}, Gaurav Chopra^{1

1}, Rena G Lapidus³, Herman O Sintim^{1

2

1

1}

Affiliations

¹ Institute for Drug Discovery, Department of Chemistry, Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
² Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.
³ Translational Core Laboratory, University of Maryland Greenebaum Cancer Center, 655 West Baltimore Street, Baltimore, Maryland 21201, United States.

Abstract

Acute myeloid leukemia (AML) is an aggressive malignancy with only a handful of therapeutic options. About 30% of AML patients harbor mutated FLT3 kinase, and thus, this cancer-driver has become a hotly pursued AML target. Herein we report a new class of FLT3 inhibitors, which potently inhibit the proliferation of acute myeloid leukemia (AML) cells at nanomolar concentrations.

Keywords: FMS-like tyrosine kinase 3 (FLT3); acute myeloid leukemia (AML); azo; click-it/staple-it; inhibitor.

Grants and funding

P30 CA023168/CA/NCI NIH HHS/United States