2QD9

P38 Alpha Map Kinase inhibitor based on heterobicyclic scaffolds

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Synthesis and SAR of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds.

Murali Dhar, T.G., Wrobleski, S.T., Lin, S., Furch, J.A., Nirschl, D.S., Fan, Y., Todderud, G., Pitt, S., Doweyko, A.M., Sack, J.S., Mathur, A., McKinnon, M., Barrish, J.C., Dodd, J.H., Schieven, G.L., Leftheris, K.

(2007) Bioorg Med Chem Lett 17: 5019-5024

  • DOI: https://doi.org/10.1016/j.bmcl.2007.07.029
  • Primary Citation of Related Structures:  
    2QD9

  • PubMed Abstract: 

    The synthesis and structure-activity relationships (SAR) of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38alpha MAP kinase with good cellular potency toward the inhibition of TNF-alpha production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38alpha is also disclosed.

    • Organizational Affiliation: 

    Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. [email protected]


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: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LGF
Query on LGF
Download Ideal Coordinates CCD File 
B [auth A]1-[5-[[3-[2,4-bis(fluoranyl)phenyl]-6,8-dihydro-5~{H}-imidazo[1,5-a]pyrazin-7-yl]carbonyl]-6-methoxy-1~{H}-pyrrolo[2,3-b]pyridin-3-yl]-2-[(3~{R})-3-oxidanylpyrrolidin-1-yl]ethane-1,2-dione
C27 H24 F2 N6 O5
GRRHHDRNCLEFSY-MRXNPFEDSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LGF BindingDB:  2QD9 IC50: 13 (nM) from 1 assay(s)
PDBBind:  2QD9 IC50: 13 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.65α = 90
b = 74.36β = 90
c = 78.98γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2007-08-21 
    • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2007-08-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-12-12
    Changes: Advisory, Data collection, Derived calculations, Refinement description, Structure summary
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations, Refinement description