title: HER-2-directed, small-molecule antagonists.
abstract: Inactivation of the human epidermal growth factor receptor-2 (HER-2) tyrosine kinase holds significant promise as a cancer treatment hypothesis, making it a high-value target for drug discovery. Screening and structure-based efforts have led to the development of several classes of ATP analog inhibitors of the HER-2 tyrosine kinase. These efforts have been further enhanced by detailed structural information regarding its sibling kinase, the EGF receptor, and structural properties that can be exploited to confer activity and even selectivity toward HER-2 kinase. Signaling and structural studies also suggest a critical involvement of the kinase inactive HER-3 in the regulation of HER-2, creating unique challenges in the efforts to inactivate the latter.
authors.affiliation: Department of Medicine and Comprehensive Cancer Center, Box 0875, San Francisco, CA 94143-0875, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Arkin
authors.forename: Mark M
authors.initials: MM
authors.lastname: Moasser
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D015507:Drugs, Investigational; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human