title: Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR.
abstract: A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based on a tri-substituted triazine scaffold has led to the discovery of potent and selective inhibitors of mTOR.
authors.affiliation: KuDOS Pharmaceuticals Ltd, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0PE, UK.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Menear
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gomez
authors.forename: Karine
authors.initials: K
authors.lastname: Malagu
authors.forename: Christine
authors.initials: C
authors.lastname: Bailey
authors.forename: Kristel
authors.initials: K
authors.lastname: Blackburn
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Cockcroft
authors.forename: Sally
authors.initials: S
authors.lastname: Ewen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fundo
authors.forename: Armelle
authors.initials: A
authors.lastname: Le Gall
authors.forename: Gesine
authors.initials: G
authors.lastname: Hermann
authors.forename: Luisa
authors.initials: L
authors.lastname: Sebastian
authors.forename: Mihiro
authors.initials: M
authors.lastname: Sunose
authors.forename: Thomas
authors.initials: T
authors.lastname: Presnot
authors.forename: Eleanor
authors.initials: E
authors.lastname: Torode
authors.forename: Ian
authors.initials: I
authors.lastname: Hickson
authors.forename: Niall M B
authors.initials: NM
authors.lastname: Martin
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Smith
authors.forename: Kurt G
authors.initials: KG
authors.lastname: Pike
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D011743:Pyrimidines; D058570:TOR Serine-Threonine Kinases; D014227:Triazines; C546842:MTOR protein, human