6AYD

Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.171 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

From PIM1 to PI3K delta via GSK3 beta : Target Hopping through the Kinome.

Henley, Z.A.Bax, B.D.Inglesby, L.M.Champigny, A.Gaines, S.Faulder, P.Le, J.Thomas, D.A.Washio, Y.Baldwin, I.R.

(2017) ACS Med Chem Lett 8: 1093-1098

  • DOI: https://doi.org/10.1021/acsmedchemlett.7b00296
  • Primary Citation of Related Structures:  
    5OY4, 6AYD

  • PubMed Abstract: 

    Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3β through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kδ activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure-activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K isoforms.


  • Organizational Affiliation

    Refractory Respiratory Inflammation DPU, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, SG1 2NY, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase pim-1334Homo sapiensMutation(s): 1 
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
C2J
Query on C2J

Download Ideal Coordinates CCD File 
B [auth A]N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide
C17 H15 N3 O2
RXQXACYMRVINQU-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.171 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.3α = 90
b = 97.3β = 90
c = 80.221γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data 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: 2017-12-27
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description