3P7A

p38 inhibitor-bound

Summary for 3P7A

• Entry DOI: 10.2210/pdb3p7a/pdb
• Related: 3P5K 3P78 3P79 3P7B 3P7C
• Descriptor: Mitogen-activated protein kinase 14, octyl beta-D-glucopyranoside, 1-[5-tert-butyl-2-(1,1-dioxidothiomorpholin-4-yl)thiophen-3-yl]-3-naphthalen-1-ylurea, ... (4 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 42849.95

Authors

Moffett, K.K.,Namboodiri, H. (deposition date: 2010-10-12, release date: 2011-10-12, Last modification date: 2024-02-21)

Primary citation

Moffett, K.,Konteatis, Z.,Nguyen, D.,Shetty, R.,Ludington, J.,Fujimoto, T.,Lee, K.J.,Chai, X.,Namboodiri, H.,Karpusas, M.,Dorsey, B.,Guarnieri, F.,Bukhtiyarova, M.,Springman, E.,Michelotti, E.
Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).
Bioorg.Med.Chem.Lett., 21:7155-7165, 2011

PubMed Abstract: Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

PubMed: 22014550
DOI: 10.1016/j.bmcl.2011.09.078

Experimental method

X-RAY DIFFRACTION (2.31 Å)