title: Discovery of a new class of glucosylceramide synthase inhibitors.
abstract: A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo.
authors.affiliation: Exelixis, 210 E. Grand Avenue, South San Francisco, CA 94005, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Koltun
authors.forename: Steven
authors.initials: S
authors.lastname: Richards
authors.forename: Vicky
authors.initials: V
authors.lastname: Chan
authors.forename: Jason
authors.initials: J
authors.lastname: Nachtigall
authors.forename: Hongwang
authors.initials: H
authors.lastname: Du
authors.forename: Kevin
authors.initials: K
authors.lastname: Noson
authors.forename: Adam
authors.initials: A
authors.lastname: Galan
authors.forename: Naing
authors.initials: N
authors.lastname: Aay
authors.forename: Art
authors.initials: A
authors.lastname: Hanel
authors.forename: Amanda
authors.initials: A
authors.lastname: Harrison
authors.forename: Jeff
authors.initials: J
authors.lastname: Zhang
authors.forename: Kwang-Ai
authors.initials: KA
authors.lastname: Won
authors.forename: Danny
authors.initials: D
authors.lastname: Tam
authors.forename: Fawn
authors.initials: F
authors.lastname: Qian
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Patricia
authors.initials: P
authors.lastname: Finn
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ogilvie
authors.forename: Jon
authors.initials: J
authors.lastname: Rosen
authors.forename: Raju
authors.initials: R
authors.lastname: Mohan
authors.forename: Christopher
authors.initials: C
authors.lastname: Larson
authors.forename: Peter
authors.initials: P
authors.lastname: Lamb
authors.forename: John
authors.initials: J
authors.lastname: Nuss
authors.forename: Patrick
authors.initials: P
authors.lastname: Kearney
mesh_terms: D000284:Administration, Oral; D000818:Animals; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase