3PRF

Crystal Structure of Human B-Raf Kinase Domain in Complex with a Non-Oxime Furopyridine Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.269 
  • R-Value Observed: 0.271 

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Ligand Structure Quality Assessment 


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


Literature

Non-oxime inhibitors of B-Raf(V600E) kinase.

Ren, L., Wenglowsky, S., Miknis, G., Rast, B., Buckmelter, A.J., Ely, R.J., Schlachter, S., Laird, E.R., Randolph, N., Callejo, M., Martinson, M., Galbraith, S., Brandhuber, B.J., Vigers, G., Morales, T., Voegtli, W.C., Lyssikatos, J.

(2011) Bioorg Med Chem Lett 21: 1243-1247

  • DOI: https://doi.org/10.1016/j.bmcl.2010.12.061
  • Primary Citation of Related Structures:  
    3PPJ, 3PPK, 3PRF, 3PRI

  • PubMed Abstract: 

    The development of inhibitors of B-Raf(V600E) serine-threonine kinase is described. Various head-groups were examined to optimize inhibitor activity and ADME properties. Several of the head-groups explored, including naphthol, phenol and hydroxyamidine, possessed good activity but had poor pharmacokinetic exposure in mice. Exposure was improved by incorporating more metabolically stable groups such as indazole and tricyclic pyrazole, while indazole could also be optimized for good cellular activity.

    • Organizational Affiliation: 

    Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase B-raf
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
FP3
Query on FP3
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		2-chloro-5-{[2-(pyrimidin-2-yl)furo[2,3-c]pyridin-3-yl]amino}phenol
C17 H11 Cl N4 O2
XNYZWJDKGDUFBJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FP3 PDBBind:  3PRF IC50: 1.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.269 
  • R-Value Observed: 0.271 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.188α = 90
b = 100.188β = 90
c = 164.606γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations