ci6b00711_si_001.pdf (429.06 kB)
In Search of Novel CDK8 Inhibitors by Virtual Screening
journal contribution
posted on 2017-02-13, 00:00 authored by Malika Kumarasiri, Theodosia Teo, Mingfeng Yu, Stephen Philip, Sunita K. C. Basnet, Hugo Albrecht, Matthew J. Sykes, Peng Wang, Shudong WangAberrant
activity of cyclin-dependent kinase (CDK) 8 is implicated
in various cancers. While CDK8-targeting anticancer drugs are highly
sought-after, no CDK8 inhibitor has yet reached clinical trials. Herein
a large library of drug-like molecules was computationally screened
using two complementary cascades to identify potential CDK8 inhibitors.
Thirty-three hits were identified to inhibit CDK8 and seven of them
were active against colorectal cancer cell lines. Finally, the primary
target was confirmed using three promising hits.