3LCO

Inhibitor Bound to A DFG-Out structure of the Kinase Domain of CSF-1R


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.289 
  • R-Value Work: 0.245 
  • R-Value Observed: 0.247 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode.

Meyers, M.J.Pelc, M.Kamtekar, S.Day, J.Poda, G.I.Hall, M.K.Michener, M.L.Reitz, B.A.Mathis, K.J.Pierce, B.S.Parikh, M.D.Mischke, D.A.Long, S.A.Parlow, J.J.Anderson, D.R.Thorarensen, A.

(2010) Bioorg Med Chem Lett 20: 1543-1547

  • DOI: https://doi.org/10.1016/j.bmcl.2010.01.078
  • Primary Citation of Related Structures:  
    3LCD, 3LCO

  • PubMed Abstract: 

    The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.


  • Organizational Affiliation

    Pfizer Global Research & Development, St. Louis Laboratories, 700 Chesterfield Parkway West, Chesterfield, MO 63017, United States. marvin.j.meyers@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Macrophage colony-stimulating factor 1 receptor324Homo sapiensMutation(s): 0 
Gene Names: CSF-1RCSF1RFMS
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P07333 (Homo sapiens)
Explore P07333 
Go to UniProtKB:  P07333
PHAROS:  P07333
GTEx:  ENSG00000182578 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07333
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LC0
Query on LC0

Download Ideal Coordinates CCD File 
B [auth A]3-({4-methoxy-5-[(4-methoxybenzyl)oxy]pyridin-2-yl}methoxy)-5-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-amine
C23 H24 N6 O4
FYNJLBSSIPLISK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LC0 PDBBind:  3LCO IC50: 143 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.289 
  • R-Value Work: 0.245 
  • R-Value Observed: 0.247 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.916α = 90
b = 62.916β = 90
c = 183.943γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-15
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-16
    Changes: Refinement description, Source and taxonomy
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations