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.

Naked Discovery

Unlike the highest secrecy in closed-door traditional drug discovery by the pool of rigid mindset scientists, the Open Source Drug Discovery (OSSD) Program aims to address the issue by capturing the youngest and brightest minds around the globe to be a part of developing drugs to treat diseases such as drug-resistant TB and malaria, and HIV. Open-source software may have been around for many years, but using an open-source model to speed up drug discovery is a relatively new idea

"Research labs in India are filled more with technicians, as opposed to creative minds. "You really don’t need to have a doctorate in pharmacy to contribute to developing a drug" said Samir Brahmachari, Director General of India’s Council of Scientific and Industrial Research (CSIR), and he believes that the OSDD can be as successful as Linux or a Wikipedia.

Tuberculosis kills at least 3,30,000 Indians annually and 1.7 million people Globally. The incidence of multi- and extensively drug-resistant strains of TB ( MRD- and XRD- TB ) demands renewed efforts to develop a novel class of fast-acting anti TB chemotherapeutics. Recently, Indian scientists have mapped the Mtb tuberculosis genome under the OSDD initiative of CSIR, giving hope of discovering new drugs for TB. This is the first time that the Mtb genome's comprehensive mapping has been accumulated, confirmed, and made available publicly.

This Connect to decode‘S (C2D) finding may contain critical data to unlock previously undiscovered details of TB, resulting in development opportunities for urgently needed new drugs in India and other developing countries.