4GRB

Casein kinase 2 (CK2) bound to inhibitor

Summary for 4GRB

• Entry DOI: 10.2210/pdb4grb/pdb
• Related: 3U4U
• Descriptor: Casein kinase II subunit alpha, CHLORIDE ION, 5-(2-{[4-(dimethylcarbamoyl)phenyl]amino}-4-methoxypyrimidin-5-yl)thiophene-3-carboxylic acid, ... (4 entities in total)
• Functional Keywords: kinase, protein kinase, cytosol, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 40312.39

Authors

Larsen, N.A.,Dowling, J.E.,Ferguson, A.D. (deposition date: 2012-08-24, release date: 2013-08-28, Last modification date: 2024-02-28)

Primary citation

Dowling, J.E.,Alimzhanov, M.,Bao, L.,Block, M.H.,Chuaqui, C.,Cooke, E.L.,Denz, C.R.,Hird, A.,Huang, S.,Larsen, N.A.,Peng, B.,Pontz, T.W.,Rivard-Costa, C.,Saeh, J.C.,Thakur, K.,Ye, Q.,Zhang, T.,Lyne, P.D.
Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo.
ACS Med Chem Lett, 4:800-805, 2013

PubMed Abstract: In this letter, we describe the design, synthesis, and structure-activity relationship of 5-anilinopyrazolo[1,5-a]pyrimidine inhibitors of CK2 kinase. Property-based optimization of early leads using the 7-oxetan-3-yl amino group led to a series of matched molecular pairs with lower lipophilicity, decreased affinity for human plasma proteins, and reduced binding to the hERG ion channel. Agents in this study were shown to modulate pAKT(S129), a direct substrate of CK2, in vitro and in vivo, and exhibited tumor growth inhibition when administered orally in a murine DLD-1 xenograft.

PubMed: 24900749
DOI: 10.1021/ml400197u

Experimental method

X-RAY DIFFRACTION (2.15 Å)