title: Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors.
abstract: The phosphoinositide 3-kinases (PI3Ks) constitute an important family of lipid kinase enzymes that control a range of cellular processes through their regulation of a network of signal transduction pathways, and have emerged as important therapeutic targets in the context of cancer, inflammation and cardiovascular diseases. Since the mid-late 1990s, considerable progress has been made in the discovery and development of small molecule ATP-competitive PI3K inhibitors, a number of which have entered early phase human trials over recent years from which key clinical results are now being disclosed. This review summarizes progress made to date, primarily on the discovery and characterization of class I and dual class I/IV subtype inhibitors, together with advances that have been made in translational and clinical research, notably in cancer.
authors.affiliation: Karus Therapeutics Ltd., Southampton Science Park, Southampton, SO16 7NP, UK. s.shuttleworth@karustherapeutics.com
authors.forename: S J
authors.initials: SJ
authors.lastname: Shuttleworth
authors.forename: F A
authors.initials: FA
authors.lastname: Silva
authors.forename: A R L
authors.initials: AR
authors.lastname: Cecil
authors.forename: C D
authors.initials: CD
authors.lastname: Tomassi
authors.forename: T J
authors.initials: TJ
authors.lastname: Hill
authors.forename: F I
authors.initials: FI
authors.lastname: Raynaud
authors.forename: P A
authors.initials: PA
authors.lastname: Clarke
authors.forename: P
authors.initials: P
authors.lastname: Workman
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015510:Clinical Medicine / Q000379:methods* / Q000639:trends; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D058534:Class I Phosphatidylinositol 3-Kinases