3PSD

Non-oxime pyrazole based inhibitors of B-Raf kinase

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.60 Å
  • R-Value Free: 0.335 
  • R-Value Work: 0.277 
  • R-Value Observed: 0.280 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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


Literature

Non-oxime pyrazole based inhibitors of B-Raf kinase.

Newhouse, B.J., Hansen, J.D., Grina, J., Welch, M., Topalov, G., Littman, N., Callejo, M., Martinson, M., Galbraith, S., Laird, E.R., Brandhuber, B.J., Vigers, G., Morales, T., Woessner, R., Randolph, N., Lyssikatos, J., Olivero, A.

(2011) Bioorg Med Chem Lett 21: 3488-3492

  • DOI: https://doi.org/10.1016/j.bmcl.2010.12.038
  • Primary Citation of Related Structures:  
    3PSD

  • PubMed Abstract: 

    The synthesis and biological evaluation of non-oxime pyrazole based B-Raf inhibitors is reported. Several oxime replacements have been prepared and have shown excellent enzyme activity. Further optimization of fused pyrazole 2a led to compound 38, a selective and potent B-Raf inhibitor.

    • Organizational Affiliation: 

    Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, United States. bnewhouse@arraybiopharma.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
307Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SM7
Query on SM7
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		6-[1-(piperidin-4-yl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl]indeno[1,2-c]pyrazole
C23 H20 N6
INSHJFDTYUIUOG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SM7 PDBBind:  3PSD IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.60 Å
  • R-Value Free: 0.335 
  • R-Value Work: 0.277 
  • R-Value Observed: 0.280 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.98α = 90
b = 94.98β = 90
c = 161.73γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description