3TXO

PKC eta kinase in complex with a naphthyridine

Summary for 3TXO

• Entry DOI: 10.2210/pdb3txo/pdb
• Descriptor: Protein kinase C eta type, 2-methyl-N~1~-[3-(pyridin-4-yl)-2,6-naphthyridin-1-yl]propane-1,2-diamine (3 entities in total)
• Functional Keywords: kinase, phosphotransferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 40786.46

Authors

Stark, W.,Rummel, G.,Cowan-Jacob, S.W. (deposition date: 2011-09-23, release date: 2011-11-30, Last modification date: 2024-11-20)

Primary citation

van Eis, M.J.,Evenou, J.P.,Floersheim, P.,Gaul, C.,Cowan-Jacob, S.W.,Monovich, L.,Rummel, G.,Schuler, W.,Stark, W.,Strauss, A.,Matt, A.,Vangrevelinghe, E.,Wagner, J.,Soldermann, N.
2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes.
Bioorg.Med.Chem.Lett., 21:7367-7372, 2011

PubMed Abstract: The present study describes a novel series of ATP-competitive PKC inhibitors based on the 2,6-naphthyridine template. Example compounds potently inhibit the novel Protein Kinase C (PKC) isotypes δ, ε, η, θ (in particular PKCε/η, and display a 10-100-fold selectivity over the classical PKC isotypes. The prototype compound 11 was found to inhibit PKCθ-dependent pathways in vitro and in vivo. In vitro, a-CD3/a-CD28-induced lymphocyte proliferation could be effectively blocked in 10% rat whole blood. In mice, 11 dose-dependently inhibited Staphylococcus aureus enterotoxin B-triggered IL-2 serum levels after oral dosing.

PubMed: 22078216
DOI: 10.1016/j.bmcl.2011.10.025

Experimental method

X-RAY DIFFRACTION (2.05 Å)