Premium
Discovery of NVP‐LEQ506, a Second‐Generation Inhibitor of Smoothened
Author(s) -
Peukert Stefan,
He Feng,
Dai Miao,
Zhang Rui,
Sun Yingchuan,
MillerMoslin 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
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300217
Subject(s) - smoothened , pharmacology , potency , antagonist , chemistry , medicine , hedgehog signaling pathway , in vitro , biochemistry , receptor , signal transduction
First disclosure: 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.