Tuesday, April 27, 2010

Kinase Inhibitors: beyond Oncology

We just published a paper in Bioorganic and Medicinal Chemistry, targeting Interleukin-2 inducible T-cell kinase (ITK) for treating Asthma.
Protein kinases are prime targets for anticancer therapies, but achieving specificity for a particular kinase is challenging because of their close structural similarities. This leads to unwanted side effects and the toxic outcome may also be due the result of tissue distribution of kinase inhibitors. Imatinib has been highly successful in the treatment of both chronic myelogenous leukaemia , gastrointestinal stromal tumours and other cancers,but associated with severe, cardio toxicity. Toxicity may be of less concern with oncologic kinases, What about non- cancer indications? Emerging clinical evidence (Nature Drug Discovery) of oral kinase inhibitors other than cancer shows that kinases could be effective at inhibiting number of inflammatory pathways.

Almost all the p38MAPK inhibitors having hepatotoxicity issue, SCIO 469 and Arry 797 initially developed for RA but went in to clinic for post operative dental pain , here the potential toxicity problems won’t show up because the drugs is used only for a very short time, Are BMS-582949 and VX 702 still in development? Hundreds of millions have been spent by different companies on P38 with nothing to show at the end.

Tasocitinib may be the first kinase inhibitor (JAK3) for non-oncology indication and the first oral DMARD for RA in a decade, if it successfully completes the Phase III

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