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Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2010 Mar 16; Vol. 1 (3), pp. 130-4. Date of Electronic Publication: 2010 Mar 16 (Print Publication: 2010). - Publication Year :
- 2010
-
Abstract
- The blockade of aberrant hedgehog (Hh) signaling has shown promise for therapeutic intervention in cancer. A cell-based phenotypic high-throughput screen was performed, and the lead structure (1) was identified as an inhibitor of the Hh pathway via antagonism of the Smoothened receptor (Smo). Structure-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl-3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 1
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 24900187
- Full Text :
- https://doi.org/10.1021/ml1000307