Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2

Zhe Nie; Carin Perretta; Philip Erickson; Stephen Margosiak; Robert Almassy; Jia Lu; April Averill; Kraig M Yager; Shaosong Chu

doi:10.1016/j.bmcl.2007.05.041

Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4191-5. doi: 10.1016/j.bmcl.2007.05.041. Epub 2007 May 18.

Authors

Zhe Nie¹, Carin Perretta, Philip Erickson, Stephen Margosiak, Robert Almassy, Jia Lu, April Averill, Kraig M Yager, Shaosong Chu

Affiliation

¹ Department of Medicinal Chemistry, Polaris Pharmaceuticals Inc., San Diego, CA 92121, USA. [email protected]

PMID: 17540560
DOI: 10.1016/j.bmcl.2007.05.041

Abstract

The structure-based design, synthesis, and anticancer activity of novel inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series of modifications provided pM inhibitors with microM-level cytotoxic activity in cell-based assays with prostate and colon cancer cell lines.

MeSH terms

Binding Sites
Casein Kinase II / antagonists & inhibitors*
Casein Kinase II / metabolism
Cell Line, Tumor
Crystallography, X-Ray
Drug Design
Humans
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*

Substances

Protein Kinase Inhibitors
Casein Kinase II