Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation

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...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2013-07, Vol.23 (13), p.3741-3748
Hauptverfasser:	Furet, Pascal, Guagnano, Vito, Fairhurst, Robin A., Imbach-Weese, Patricia, Bruce, Ian, Knapp, Mark, Fritsch, Christine, Blasco, Francesca, Blanz, Joachim, Aichholz, Reiner, Hamon, Jacques, Fabbro, Doriano, Caravatti, Giorgio
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals antineoplastic agents Antitumor agent Biological Availability Cell Line chemistry Dogs Dose-Response Relationship, Drug Drug Discovery Female Humans Mice Models, Molecular Molecular Structure phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Phosphorylation - drug effects PI3K inhibitors Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Sprague-Dawley Structure-Activity Relationship Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacology
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Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2013.05.007