Virtual Screening to Successfully Identify Novel Janus Kinase 3 Inhibitors: A Sequential Focused Screening Approach
Xin Chen, Lawrence J. Wilson, Ravi Malaviya, Rochelle L. Argentieri, Shyh‐Ming Yang · Journal of Medicinal Chemistry · 2008
In an effort to identify novel Janus kinase 3 inhibitors, a sequential focused screening approach was adopted to search our in-house chemical database. By biologically testing only 79 selected compounds, we successfully identified 19 compounds showing IC 50 < 20 microM, with four of them in the nanomolar range. Particularly, a 3,5-disubstituted pyrazolo[4,3- d]pyrimidine scaffold emerged as a promising candidate for further lead optimization. With the advantages of efficiency and flexibility, this approach may be utilized to identify leads for other therapeutic targets.