3F5X

CDK-2-Cyclin complex with indazole inhibitor 9 bound at its active site

Summary for 3F5X

• Entry DOI: 10.2210/pdb3f5x/pdb
• Descriptor: Cell division protein kinase 2, Cyclin-A2, GLYCEROL, ... (6 entities in total)
• Functional Keywords: kinase, pkc, protein kinase, inhibitor, atp-binding, cell cycle, cell division, mitosis, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, cyclin, nucleus, transferase-cell cycle complex, transferase/cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P20248
• Total number of polymer chains: 4
• Total formula weight: 127936.36

Authors

Kiefer, J.R.,Day, J.E.,Caspers, N.L.,Mathis, K.J.,Kretzmer, K.K.,Weinberg, R.A.,Reitz, B.A.,Stegeman, R.A.,Trujillo, J.I.,Huang, W.,Thorarensen, A.,Xing, L.,Wrightstone, A.,Christine, L.,Compton, R.,Li, X. (deposition date: 2008-11-04, release date: 2009-02-03, Last modification date: 2023-12-27)

Primary citation

Trujillo, J.I.,Kiefer, J.R.,Huang, W.,Thorarensen, A.,Xing, L.,Caspers, N.L.,Day, J.E.,Mathis, K.J.,Kretzmer, K.K.,Reitz, B.A.,Weinberg, R.A.,Stegeman, R.A.,Wrightstone, A.,Christine, L.,Compton, R.,Li, X.
2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: Design and synthesis of a potent and isoform selective PKC-zeta inhibitor.
Bioorg.Med.Chem.Lett., 19:908-911, 2009

PubMed Abstract: The inhibition of PKC-zeta has been proposed to be a potential drug target for immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). The determination of the crystal structures of key inhibitor:CDK-2 complexes informed the design and analysis of the series. The most selective and potent analog was identified by variation of the aryl substituent at the 6-position of the indazole template to give a 4-NH(2) derivative. The analog displays good selectivity over other PKC isoforms (alpha, betaII, gamma, delta, epsilon, mu, theta, eta and iota/lambda) and CDK-2, however it displays marginal selectivity against a panel of other kinases (37 profiled).

PubMed: 19097791
DOI: 10.1016/j.bmcl.2008.11.105

Experimental method

X-RAY DIFFRACTION (2.4 Å)