title: A novel phosphotyrosine mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp): exploitation in the design of nonpeptide inhibitors of pp60(Src) SH2 domain.
abstract: The novel phosphotyrosine (pTyr) mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp) has been designed and incorporated into a series of nonpeptide inhibitors of the SH2 domain of pp60(c-Src) (Src) tyrosine kinase. A 2.2 A X-ray crystal structure of 1a bound to a mutant form of Lck SH2 domain provides insight regarding the structure-activity relationships and supports the design concept of this new pTyr mimetic.
authors.affiliation: ARIAD Pharmaceuticals, Inc., Cambridge, MA 02139-4234, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kawahata
authors.forename: M G
authors.initials: MG
authors.lastname: Yang
authors.forename: G P
authors.initials: GP
authors.lastname: Luke
authors.forename: W C
authors.initials: WC
authors.lastname: Shakespeare
authors.forename: R
authors.initials: R
authors.lastname: Sundaramoorthi
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Johnson
authors.forename: T
authors.initials: T
authors.lastname: Merry
authors.forename: S
authors.initials: S
authors.lastname: Violette
authors.forename: W
authors.initials: W
authors.lastname: Guan
authors.forename: C
authors.initials: C
authors.lastname: Bartlett
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Hatada
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: D C
authors.initials: DC
authors.lastname: Dalgarno
authors.forename: C J
authors.initials: CJ
authors.lastname: Eyermann
authors.forename: R S
authors.initials: RS
authors.lastname: Bohacek
authors.forename: T K
authors.initials: TK
authors.lastname: Sawyer
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D001862:Bone Resorption; D018360:Crystallography, X-Ray; D003804:Dentin / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D009154:Mutation; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D019000:Phosphotyrosine / Q000737:chemistry*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011817:Rabbits; D013329:Structure-Activity Relationship; D018909:src Homology Domains / Q000187:drug effects*
chemical_list: C442382:4-(2-acetamido-3-(1-(3-carbamoyl-4-(cyclohexylmethoxy)phenyl)ethylamino)-3-oxopropyl)-2-(carboxymethoxy)benzenephosphonic acid; D001549:Benzamides; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)