3OCG

P38 Alpha kinase complexed with a 5-amino-pyrazole based inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

5-Amino-pyrazoles as potent and selective p38α inhibitors

Das, J.Moquin, R.V.Dyckman, A.J.Li, T.Pitt, S.Zhang, R.Shen, D.R.McIntyre, K.W.Gillooly, K.Doweyko, A.M.Newitt, J.A.Sack, J.S.Zhang, H.Kiefer, S.E.Kish, K.McKinnon, M.Barrish, J.C.Dodd, J.H.Schieven, G.L.Leftheris, K.

(2010) Bioorg Med Chem Lett 20: 6886-6889

  • DOI: https://doi.org/10.1016/j.bmcl.2010.10.034
  • Primary Citation of Related Structures:  
    3OCG

  • PubMed Abstract: 

    The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 14366Homo sapiensMutation(s): 0 
Gene Names: CSBPCSBP1CSBP2CSPB1MAPK14MXI2
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for Q16539 (Homo sapiens)
Explore Q16539 
Go to UniProtKB:  Q16539
PHAROS:  Q16539
GTEx:  ENSG00000112062 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16539
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
OCG
Query on OCG

Download Ideal Coordinates CCD File 
B [auth A]5-amino-N-[5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl]-1-phenyl-1H-pyrazole-4-carboxamide
C21 H18 N6 O3
DMYYPSLMFSEFCK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
OCG BindingDB:  3OCG IC50: 3 (nM) from 1 assay(s)
PDBBind:  3OCG IC50: 3 (nM) from 1 assay(s)
Binding MOAD:  3OCG IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.94α = 90
b = 71.43β = 90
c = 80.55γ = 90
Software Package:
Software NamePurpose
AMoREphasing
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-11-17 
  • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-09-02
    Changes: Database references, Derived calculations, Structure summary
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references