Pan, Shifeng, Wu, Xu, Jiang, Jiqing, Gao, Wenqi, Wan, Yongqin, Cheng, Dai, Han, Dong, Englund, Nathan, Wang, Yan, Peukert, Stefan, Miller-Moslin, Karen, Williams, Juliet, Yuan, Jing, Guo, Ribo, Vattay, Anthony, Jiang, Yun, Tsao, Jeffrey, Buonamici, Silvia, Sun, Fangxian, Pferdekamper, AnneMarie, Dodd, Stephanie, Tuntland, Tove, Maniara, Wieslawa, Kelleher Iii, Joseph, Warmuth, Markus and Dorsch, Marion (2010) Discovery of NVP-LDE225, a potent and selective biphenyl-3-carboxamide smoothened antagonist. ACS Medicinal Chemistry Letters, 1 (3). pp. 130-134. ISSN 1948-5875

Abstract

Blockade of aberrant hedgehog (Hh) signaling has shown promise for therapeutic intervention in cancer. A cell-based phenotypic high throughput screen was performed, and 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.

Item Type:	Article
Additional Information:	archiving not formally supported by this publisher
Date Deposited:	13 Oct 2015 13:16
Last Modified:	13 Oct 2015 13:16
URI:	https://oak.novartis.com/id/eprint/2374