3MPM

LCK complexed with a pyrazolopyrimidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck.

Gommermann, N.Buehlmayer, P.von Matt, A.Breitenstein, W.Masuya, K.Pirard, B.Furet, P.Cowan-Jacob, S.W.Weckbecker, G.

(2010) Bioorg Med Chem Lett 20: 3628-3631

  • DOI: https://doi.org/10.1016/j.bmcl.2010.04.112
  • Primary Citation of Related Structures:  
    3MPM

  • PubMed Abstract: 

    A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency.


  • Organizational Affiliation

    Novartis Institute of Biomedical Research, Forum 1, Novartis Campus, Basel, Switzerland. nina.gommermann@novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase Lck267Homo sapiensMutation(s): 1 
Gene Names: LCK
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P06239 (Homo sapiens)
Explore P06239 
Go to UniProtKB:  P06239
PHAROS:  P06239
GTEx:  ENSG00000182866 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06239
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5LK
Query on 5LK

Download Ideal Coordinates CCD File 
B [auth A]4-{(6R,7R)-7-amino-3-[3-(4-methylpiperazin-1-yl)phenyl]-6,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl}phenol
C23 H26 N6 O
KIMZUJNGIVVWNZ-RBBKRZOGSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5LK PDBBind:  3MPM IC50: 30 (nM) from 1 assay(s)
Binding MOAD:  3MPM IC50: 30 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.073α = 90
b = 44.624β = 90
c = 120.967γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
REFMACrefinement
XDSdata reduction
XSCALEdata 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: 2010-06-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-03-07
    Changes: Data collection
  • Version 1.3: 2021-10-06
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-21
    Changes: Data collection