3D4Q

Pyrazole-based inhibitors of B-Raf kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.216 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Potent and selective pyrazole-based inhibitors of B-Raf kinase.

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

(2008) Bioorg Med Chem Lett 18: 4692-4695

  • DOI: https://doi.org/10.1016/j.bmcl.2008.07.002
  • Primary Citation of Related Structures:  
    3D4Q

  • PubMed Abstract: 

    Herein we describe a novel pyrazole-based class of ATP competitive B-Raf inhibitors. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. A subset of these inhibitors has demonstrated the ability to inhibit downstream ERK phosphorylation in LOX tumors from mouse xenograft studies.


  • Organizational Affiliation

    Lead Optimization, Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA. josh.hansen@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: BRAFBRAF1RAFB1
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
SM5
Query on SM5

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(1E)-5-(1-piperidin-4-yl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime
C22 H23 N5 O
KWEFZSZCLBHIEQ-YYADALCUSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SM5 BindingDB:  3D4Q IC50: min: 0.03, max: 9 (nM) from 2 assay(s)
PDBBind:  3D4Q IC50: 0.03 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.216 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.343α = 90
b = 100.343β = 90
c = 162.536γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-19
    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: 2024-02-21
    Changes: Data collection, Database references, Derived calculations