Cancers, Vol. 12, Pages 2327: Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors

Cancers, Vol. 12, Pages 2327: Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors Cancers doi: 10.3390/cancers12082327 Authors: Vibhu Jha Marco Macchia Tiziano Tuccinardi Giulio Poli Src family kinases (SFKs) constitute the biggest family of non-receptor tyrosine kinases considered as therapeutic targets for cancer therapy. An aberrant expression and/or activation of the proto-oncogene c-Src kinase, which is the oldest and most studied member of the family, has long been demonstrated to play a major role in the development, growth, progression and metastasis of numerous human cancers, including colon, breast, gastric, pancreatic, lung and brain carcinomas. For these reasons, the pharmacological inhibition of c-Src activity represents an effective anticancer strategy and a few compounds targeting c-Src, together with other kinases, have been approved as drugs for cancer therapy, while others are currently undergoing preclinical studies. Nevertheless, the development of potent and selective inhibitors of c-Src aimed at properly exploiting this biological target for the treatment of cancer still represents a growing field of study. In this review, the co-crystal structures of c-Src kinase in complex with inhibitors discovered in the past two decades have been described, highlighting the key ligand–protein interactions necessary to obtain high potency and the features to be exploited for addressing selectiv...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research