3II5

The Complex of wild-type B-RAF with Pyrazolo pyrimidine inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

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This is version 1.2 of the entry. See complete history. 


Literature

Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors.

Berger, D.M., Torres, N., Dutia, M., Powell, D., Ciszewski, G., Gopalsamy, A., Levin, J.I., Kim, K.H., Xu, W., Wilhelm, J., Hu, Y., Collins, K., Feldberg, L., Kim, S., Frommer, E., Wojciechowicz, D., Mallon, R.

(2009) Bioorg Med Chem Lett 19: 6519-6523

  • DOI: https://doi.org/10.1016/j.bmcl.2009.10.049
  • Primary Citation of Related Structures:  
    3II5

  • PubMed Abstract: 

    As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

    • Organizational Affiliation: 

    Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. bergerd@wyeth.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
B-Raf proto-oncogene serine/threonine-protein kinase
A, B
306Homo sapiensMutation(s): 0 
Gene Names: BRAF, BRAF1, RAFB1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P15056 (Homo sapiens)
Explore P15056 
Go to UniProtKB:  P15056
PHAROS:  P15056
GTEx:  ENSG00000157764 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15056
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
831 PDBBind:  3II5 IC50: 24 (nM) from 1 assay(s)
BindingDB:  3II5 IC50: 24 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.219α = 90
b = 110.219β = 90
c = 148.468γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
AMoREphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-11-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations