PDBsum entry 3iph

Transferase

PDB id: 3iph

Contents

Protein chain

347 a.a.

Ligands

G11

SO4

GOL ×6

Waters ×343

References listed in PDB file

Key reference

• Title: P38alpha mitogen-Activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression.
• Authors: N.M.Aston, P.Bamborough, J.B.Buckton, C.D.Edwards, D.S.Holmes, K.L.Jones, V.K.Patel, P.A.Smee, D.O.Somers, G.Vitulli, A.L.Walker.
• Ref.: J Med Chem, 2009, 52, 6257-6269.
• PubMed id: 19772287

Abstract

p38alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFalpha and IL-1beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38alpha/beta inhibitors using crystal structures of our inhibitors bound to p38alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development.