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UNC1062, a new and potent Mer inhibitor.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2013 Jul; Vol. 65, pp. 83-93. Date of Electronic Publication: 2013 Apr 02. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Dose-Response Relationship, Drug
Humans
Molecular Structure
Morpholines chemical synthesis
Morpholines chemistry
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides chemistry
c-Mer Tyrosine Kinase
Morpholines pharmacology
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins antagonists & inhibitors
Receptor Protein-Tyrosine Kinases antagonists & inhibitors
Sulfonamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 65
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23693152
- Full Text :
- https://doi.org/10.1016/j.ejmech.2013.03.035