2. Academic Validation
  3. Identification of acylthiourea derivatives as potent Plk1 PBD inhibitors

Identification of acylthiourea derivatives as potent Plk1 PBD inhibitors

  • Eur J Med Chem. 2016 Nov 29;124:229-236. doi: 10.1016/j.ejmech.2016.08.043.
Taikangxiang Yun 1,  Tan Qin 2,  Ying Liu 3,  Luhua Lai 4
Affiliations

Affiliations

  • 1 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 2 BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • 3 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: [email protected].
  • 4 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: [email protected].
PMID: 27592392 DOI: 10.1016/j.ejmech.2016.08.043
Abstract

Thiourea derivatives have drawn much attention for their latent capacities of biological activities. In this study, we designed acylthiourea compounds as polo-like kinase 1 (PLK1) polo-box domain (PBD) inhibitors. A series of acylthiourea derivatives without pan assay interference structure (PAINS) were synthesized. Four compounds with halogen substituents exhibited binding affinities to PLK1 PBD in low micromole range. The most potent compound (3v) showed selectivity over other subtypes of Plk PBDs and inhibited the kinase activity of full-length PLK1.

Keywords

Binding affinity; Halogenosulfamoylphenyl acylthiourea; In vitro assay; Polo-box domain; Polo-like kinase 1; Small molecular inhibitor.

Figures
Products