title: Synthesis and biological evaluation of desmethylveramiline, a micromolar Hedgehog inhibitor.
abstract: Desmethylveramiline (1), an aza steroid analogue of veramiline was designed as a surrogate for cyclopamine, a reference antagonist of the Sonic Hedgehog (Shh) pathway. Desmethyveramiline (1) was prepared in seven steps from commercially available Fernholtz acid using the hydroformylation of a terminal olefine as the key step for the construction of the piperidine appendage. In two assays (i) the inhibition of the Shh-induced Gli-dependent luciferase activity in Shh-light2 cells, (ii) the inhibition of the SAG-induced differentiation of the mesenchymal C3H10T1/2 cells, desmethylveramiline (1) is an inhibitor in the μM range comparable to cyclopamine.
authors: Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS-Université de Strasbourg Faculté de Pharmacie, Illkirch, France.
authors: Guillaume
authors: G
authors: Guerlet
authors: Thomas
authors: T
authors: Spangenberg
authors: André
authors: A
authors: Mann
authors: Hélène
authors: H
authors: Faure
authors: Martial
authors: M
authors: Ruat