title: In Search of Novel CDK8 Inhibitors by Virtual Screening.
abstract: Aberrant 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.
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Malika
authors.initials: M
authors.lastname: Kumarasiri
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Teo
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Philip
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Sunita K C
authors.initials: SK
authors.lastname: Basnet
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Hugo
authors.identifier: 0000-0002-3951-1866
authors.initials: H
authors.lastname: Albrecht
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Matthew J
authors.identifier: 0000-0002-2509-5531
authors.initials: MJ
authors.lastname: Sykes
authors.affiliation: Yabao Pharmaceutical Group Co., Ltd. , Suzhou Industrial Park, Suzhou, China , 215123.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Centre for Drug Discovery and Development, Sansom Institute for Health Research, Centre for Cancer Biology, and School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, South Australia 5001, Australia.
authors.forename: Shudong
authors.identifier: 0000-0001-6225-5525
authors.initials: S
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D056850:Cyclin-Dependent Kinase 8 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014584:User-Computer Interface
chemical_list: D047428:Protein Kinase Inhibitors; D056850:Cyclin-Dependent Kinase 8