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HER-2-directed, small-molecule antagonists Arkin M; Moasser MMCurr Opin Investig Drugs 2008[Dec]; 9 (12): 1264-76Inactivation 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.|Animals[MESH]|Clinical Trials as Topic[MESH]|Drug Screening Assays, Antitumor[MESH]|Drugs, Investigational/chemistry/*pharmacology/therapeutic use[MESH]|Humans[MESH]|Models, Biological[MESH]|Molecular Structure[MESH]|Receptor, ErbB-2/*antagonists & inhibitors[MESH]|Structure-Activity Relationship[MESH] |
