Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI)

  • Bioorg Med Chem Lett. 2003 Dec 15;13(24):4355-9. doi: 10.1016/j.bmcl.2003.09.028.
Juswinder Singh  1 ,  Claudio E Chuaqui ,  P Ann Boriack-Sjodin ,  Wen Cherng Lee ,  Timothy Pontz ,  Michael J Corbley ,  H-Kam Cheung ,  Robert M Arduini ,  Jonathan N Mead ,  Miki N Newman ,  James L Papadatos ,  Scott Bowes ,  Serene Josiah ,  Leona E Ling
Affiliations
PMID: 14643325 DOI: 10.1016/j.bmcl.2003.09.028
Abstract

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.