Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI).
Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee WC, Pontz T, Corbley MJ, Cheung HK, Arduini RM, Mead JN, Newman MN, Papadatos JL, Bowes S, Josiah S, Ling LE.
We describe the discovery, using shape-based virtual screening, of a potent, ATP site-directed inhibitor of the TbetaRI kinase, an important and novel drug target for fibrosis and cancer. The first detailed report of a TbetaRI kinase small molecule co-complex confirms the predicted binding interactions of our small molecule inhibitor, which stabilizes the inactive kinase conformation. Our results validate shape-based screening as a powerful tool to discover useful leads against a new drug target.