title: The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase.
abstract: We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity.
authors.affiliation: KuDOS Pharmaceuticals Ltd, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.
authors.forename: Karine
authors.initials: K
authors.lastname: Malagu
authors.forename: Heather
authors.initials: H
authors.lastname: Duggan
authors.forename: Keith
authors.initials: K
authors.lastname: Menear
authors.forename: Marc
authors.initials: M
authors.lastname: Hummersone
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gomez
authors.forename: Christine
authors.initials: C
authors.lastname: Bailey
authors.forename: Peter
authors.initials: P
authors.lastname: Edwards
authors.forename: Jan
authors.initials: J
authors.lastname: Drzewiecki
authors.forename: Frédéric
authors.initials: F
authors.lastname: Leroux
authors.forename: Mar Jimenez
authors.initials: MJ
authors.lastname: Quesada
authors.forename: Gesine
authors.initials: G
authors.lastname: Hermann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Maine
authors.forename: Carrie-Anne
authors.initials: CA
authors.lastname: Molyneaux
authors.forename: Armelle
authors.initials: A
authors.lastname: Le Gall
authors.forename: James
authors.initials: J
authors.lastname: Pullen
authors.forename: Ian
authors.initials: I
authors.lastname: Hickson
authors.forename: Lisa
authors.initials: L
authors.lastname: Smith
authors.forename: Sharon
authors.initials: S
authors.lastname: Maguire
authors.forename: Niall
authors.initials: N
authors.lastname: Martin
authors.forename: Graeme
authors.initials: G
authors.lastname: Smith
authors.forename: Martin
authors.initials: M
authors.lastname: Pass
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C493245:CRTC2 protein, human; D003959:Diamines; D009025:Morpholines; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011743:Pyrimidines; D014157:Transcription Factors; C541932:Ku 0063794; D011494:Protein Kinases; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases