期刊
DRUG DISCOVERY TODAY
卷 18, 期 19-20, 页码 992-1000出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2013.06.001
关键词
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资金
- Cyclofluidic Limited
- University of York
The story of the inhibition of BCR-ABL as a treatment for chronic myelogenous leukaemia serves to illustrate key aspects of the kinase drug discovery and development process. Firstly, elucidation of the disease mechanism enabled identification of the molecular target(s) which catalysed pharmaceutical research and resulted in Gleevec (R) (Novartis) as the first FDA approved BCR-ABL inhibitor. However, clinical success was soon tempered by the emergence of drug resistance through various mechanisms. Using rational drug design, several hypotheses were devised to overcome resistance issues leading to the development of second generation inhibitors, providing clinicians and patients with greater therapeutic choice.
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