AI Article Synopsis
- The inhibition of BCR-ABL as a treatment for chronic myelogenous leukaemia highlights the importance of understanding disease mechanisms to identify effective drug targets, leading to the development of Gleevec(®), the first FDA-approved BCR-ABL inhibitor.
- The initial success of Gleevec(®) faced challenges due to the emergence of drug resistance, which complicated treatment outcomes.
- In response, researchers employed rational drug design to create second-generation inhibitors, expanding treatment options for clinicians and patients dealing with resistance.
Article Abstract
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(®) (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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| http://dx.doi.org/10.1016/j.drudis.2013.06.001 | DOI Listing |
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