3P2B

Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.187 

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Ligand Structure Quality Assessment 


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Literature

Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors.

Pecchi, S.Renhowe, P.A.Taylor, C.Kaufman, S.Merritt, H.Wiesmann, M.Shoemaker, K.R.Knapp, M.S.Ornelas, E.Hendrickson, T.F.Fantl, W.Voliva, C.F.

(2010) Bioorg Med Chem Lett 20: 6895-6898

  • DOI: https://doi.org/10.1016/j.bmcl.2010.10.021
  • Primary Citation of Related Structures:  
    3P2B

  • PubMed Abstract: 

    PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described.


  • Organizational Affiliation

    Novartis Institutes for Biomedical Research, Emeryville, CA, USA. sabina.pecchi@novartis.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 isoform966Homo sapiensMutation(s): 1 
Gene Names: PIK3CGPK3CG
EC: 2.7.1.153
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P2B
Query on P2B

Download Ideal Coordinates CCD File 
B [auth A]3-[2-morpholin-4-yl-6-(pyridin-3-ylamino)pyrimidin-4-yl]phenol
C19 H19 N5 O2
VPAXYWZGMCIWNR-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.187 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 141.12α = 90
b = 66.78β = 96.95
c = 105.97γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
BOSdata collection

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-08-17
    Type: Initial release
  • Version 1.1: 2024-02-21
    Changes: Data collection, Database references, Derived calculations