title: Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation.
abstract: Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kα, a medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719.
authors.affiliation: Novartis Institutes for BioMedical Research, WKL-136.4.12, CH-4002 Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Vito
authors.initials: V
authors.lastname: Guagnano
authors.forename: Robin A
authors.initials: RA
authors.lastname: Fairhurst
authors.forename: Patricia
authors.initials: P
authors.lastname: Imbach-Weese
authors.forename: Ian
authors.initials: I
authors.lastname: Bruce
authors.forename: Mark
authors.initials: M
authors.lastname: Knapp
authors.forename: Christine
authors.initials: C
authors.lastname: Fritsch
authors.forename: Francesca
authors.initials: F
authors.lastname: Blasco
authors.forename: Joachim
authors.initials: J
authors.lastname: Blanz
authors.forename: Reiner
authors.initials: R
authors.lastname: Aichholz
authors.forename: Jacques
authors.initials: J
authors.lastname: Hamon
authors.forename: Doriano
authors.initials: D
authors.lastname: Fabbro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Caravatti
mesh_terms: D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005260:Female; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013844:Thiazoles; C585539:Alpelisib