3T9I

Pim1 complexed with a novel 3,6-disubstituted indole at 2.6 Ang Resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.165 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases.

Nishiguchi, G.A.Atallah, G.Bellamacina, C.Burger, M.T.Ding, Y.Feucht, P.H.Garcia, P.D.Han, W.Klivansky, L.Lindvall, M.

(2011) Bioorg Med Chem Lett 21: 6366-6369

  • DOI: https://doi.org/10.1016/j.bmcl.2011.08.105
  • Primary Citation of Related Structures:  
    3T9I

  • PubMed Abstract: 

    A series of novel 3,5-disubstituted indole derivatives as potent and selective inhibitors of all three members of the Pim kinase family is described. High throughput screen identified a pan-Pim kinase inhibitor with a promiscuous scaffold. Guided by structure-based drug design, SAR of the series afforded a highly selective indole chemotype that was further developed into a potent set of compounds against Pim-1, 2, and 3 (Pim-1 and Pim-3: IC(50)≤2nM and Pim-2: IC(50)≤100nM).


  • Organizational Affiliation

    Global Discovery Chemistry/Oncology and Exploratory Chemistry, Novartis Institutes of BioMedical Research, Emeryville, CA 94608, USA. gisele.nishiguchi@novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene serine/threonine-protein kinase pim-1328Homo sapiensMutation(s): 0 
Gene Names: PIM1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11309 (Homo sapiens)
Explore P11309 
Go to UniProtKB:  P11309
PHAROS:  P11309
GTEx:  ENSG00000137193 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11309
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3T9
Query on 3T9

Download Ideal Coordinates CCD File 
B [auth A]2-methoxy-4-(3-phenyl-2H-pyrazolo[3,4-b]pyridin-6-yl)phenol
C19 H15 N3 O2
CCYHSISZPCXEEF-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.165 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.215α = 90
b = 96.215β = 90
c = 80.245γ = 120
Software Package:
Software NamePurpose
MAR345dtbdata collection
AMoREphasing
PHENIXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-12
    Type: Initial release
  • Version 1.1: 2011-11-02
    Changes: Database references