Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2.
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.
Nie
Zhe
Z
Department of Medicinal Chemistry, Polaris Pharmaceuticals Inc., San Diego, CA 92121, USA. zhe.nie@takedasd.com
Perretta
Carin
C
Erickson
Philip
P
Margosiak
Stephen
S
Almassy
Robert
R
Lu
Jia
J
Averill
April
A
Yager
Kraig M
KM
Chu
Shaosong
S
D001665:Binding Sites; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II