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Eur J Med Chem. 2013 Jul;65:83-93. doi: 10.1016/j.ejmech.2013.03.035. Epub 2013 Apr 2.

UNC1062, a new and potent Mer inhibitor.

Author information

  • 1Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure-activity relationship studies, 35 (UNC1062) was identified as a potent (IC50 = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development.

Copyright © 2013 Elsevier Masson SAS. All rights reserved.

KEYWORDS:

Glioblastoma; KAAPXWSYROPAEL-GUAVBDGJSA-N; Leukemia; Mer inhibitors; Non-small cell lung cancer; Pyrazolopyrimidines; Sulfonamides

PMID:
23693152
[PubMed - indexed for MEDLINE]
PMCID:
PMC3720808
Free PMC Article

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