Discovery of NVP‐LEQ506, a Second‐Generation Inhibitor of Smoothened. Issue 8 (2nd July 2013)

• Record Type: Journal Article
• Authors: Peukert, Stefan; He, Feng; Dai, Miao; Zhang, Rui; Sun, Yingchuan; Miller‐Moslin, Karen; McEwan, Michael; Lagu, Bharat; Wang, Kate; Yusuff, Naeem; Bourret, Aaron; Ramamurthy, Arun; Maniara, Wieslawa; Amaral, Adam; Vattay, Anthony; Wang, Anlai; Guo, Ribo; Yuan, Jing; Green, John; Williams, Juliet; Buonamici, Silvia; Kelleher, Joseph F.; Dorsch, Marion
• Is Part Of: ChemMedChem. Volume 8:Issue 8(2013:Aug.)
• Page Start: 1261
• Page End: 1265
• Publication Date: 2013-07-02
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300217
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>First disclosure:</bold> Continued optimization provided a novel type of Smoothened (Smo) antagonist based on a pyridazine core. The compound, NVP‐LEQ506, currently in phase I clinical trials, combines high intrinsic potency and good pharmacokinetic properties resulting in excellent efficacy in rodent tumor models of medulloblastoma. Activity against a Smo mutant conferring resistance observed in a previous clinical trial with a competitor compound suggests additional therapeutic potential.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg2bfhsnzz" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>