Molecular basis of drug resistance in smoothened receptor: An in silico study of protein resistivity and specificity

Smoothened (SMO) antagonist Vismodegib effectively inhibits the Hedgehog pathway in proliferating cancer cells. In early stage of treatment, Vismodegib exhibited promising outcomes to regress the tumors cells, but ultimately relapsed due to the drug resistive mutations in SMO mostly occurring before (primary mutations G497W) or after (acquired mutations D473H/Y) anti‐SMO therapy. This study investigates the unprecedented insights of structural...