期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 65, 期 -, 页码 83-93出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.03.035
关键词
Mer inhibitors; Pyrazolopyrimidines; Sulfonamides; Leukemia; Non-small cell lung cancer; Glioblastoma
资金
- National Institute of Mental Health's Psychoactive Drug Screening Program [HHSN-271-2008-025C]
- University of North Carolina
- National Cancer Institute, National Institute of Health [HHSN261200800001E]
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. (C) 2013 Elsevier Masson SAS. All rights reserved.
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