Kinase Inhibitors: beyond Oncology

We recently 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 to the result of tissue distribution of kinase inhibitors. Imatinib has been highly successful in treating both chronic myelogenous leukemia, gastrointestinal stromal tumors, and other cancers but is associated with severe cardiotoxicity. 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 effectively inhibit the number of inflammatory pathways.

Almost all the p38MAPK inhibitors having hepatotoxicity issue. For example, SCIO 469 and Arry 797 initially developed for RA but went into the clinic for post operative dental pain; here, the potential toxicity problems will not show up because the drugs are used only for a very short time. Are BMS-582949 and VX 702 still in development? Different companies have spent hundreds of millions 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 Phase III clinical trials.