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Bioorg Med Chem Lett. 2016 May 1;26(9):2370-4. doi: 10.1016/j.bmcl.2016.03.006. Epub 2016 Mar 3.

Development of a potent and selective FLT3 kinase inhibitor by systematic expansion of a non-selective fragment-screening hit.

Author information

1
Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
2
Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. Electronic address: tlong@mol.f.u-tokyo.ac.jp.

Abstract

A non-selective inhibitor (1) of FMS-like tyrosine kinase-3 (FLT3) was identified by fragment screening and systematically modified to afford a potent and selective inhibitor 26. We confirmed that 26 inhibited the growth of FLT-3-activated human acute myeloid leukemia cell line MV4-11. Our design strategy enabled rapid development of a novel type of FLT3 inhibitor from the hit fragment in the absence of target-structural information.

KEYWORDS:

Acute myeloid leukemia; FLT3; Fragment based drug discovery; Kinase inhibitor; Kinase selectivity

PMID:
26995531
DOI:
10.1016/j.bmcl.2016.03.006
[Indexed for MEDLINE]

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