4FJY

Crystal structure of PI3K-gamma in complex with quinoline-indoline inhibitor 24f


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Discovery and in Vivo Evaluation of Dual PI3K-beta/delta inhibitors

Gonzalez-Lopez de Turiso, F.Shin, Y.Brown, M.Cardozo, M.Chen, Y.Fong, D.Hao, X.He, X.Henne, K.Hu, Y.L.Johnson, M.G.Kohn, T.Lohman, J.McBride, H.J.McGee, L.R.Medina, J.C.Metz, D.Miner, K.Mohn, D.Pattaropong, V.Seganish, J.Simard, J.L.Wannberg, S.Whittington, D.A.Yu, G.Cushing, T.D.

(2012) J Med Chem 55: 7667-7685

  • DOI: https://doi.org/10.1021/jm300679u
  • Primary Citation of Related Structures:  
    4FJY, 4FJZ

  • PubMed Abstract: 

    Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases.


  • Organizational Affiliation

    Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA. felgonza@amgen.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform960Homo sapiensMutation(s): 0 
Gene Names: PIK3CG
EC: 2.7.1.153 (PDB Primary Data), 2.7.11.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P48736 (Homo sapiens)
Explore P48736 
Go to UniProtKB:  P48736
PHAROS:  P48736
GTEx:  ENSG00000105851 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48736
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.203 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 144.223α = 90
b = 67.711β = 95.08
c = 106.772γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
DENZOdata reduction
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: 2012-10-24
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations