In Silico Hit Identification, Drug Repurposing, Pharmacokinetic and Toxicity Prediction of c-Met Kinase Inhibitors for Cancer Therapy

Cancer is globally one of the leading causes for death and through years it has been emerged to increase in the incidents of morbidity and mortality worldwide. Despite immense research and development in cancer therapy, lack of a feasible, safe and affordable treatment, opens wide scope in this area of study. Though chemotherapy is widely used for the treatment, adverse effects associated with it has brought about a step back in the therapy. Thus, targeted protein tyrosine kinase therapy has gained significance in recent times. Among the tyrosine kinase therapies, c-Met is a promising target. This target is found to be involved in tumurogenesis of different cancers and so has brought our interest towards it. c-Met belongs to the subfamily of receptor tyrosine kinases (RTKs) which are encoded by the Met proto-oncogene. This involvement of HGF/c-Met signalling pathway in oncogenesis has been reported in various types of cancers. Over expression of the target c-Met has brought about transcriptional regulation, gene amplification, autocrine or paracrine ligand stimulation leading to uncontrolled and enhanced tumor cell proliferation, survival, motility, scattering, migration, angiogenesis, invasion, epithelial-mesenchymal transition (EMT), metastatic dissemination.