3APC

Crystal structure of human PI3K-gamma in complex with CH5132799

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.54 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.239 

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This is version 1.2 of the entry. See complete history. 


Literature

Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799

Ohwada, J., Ebiike, H., Kawada, H., Tsukazaki, M., Nakamura, M., Miyazaki, T., Morikami, K., Yoshinari, K., Yoshida, M., Kondoh, O., Kuramoto, S., Ogawa, K., Aoki, Y., Shimma, N.

(2011) Bioorg Med Chem Lett 21: 1767-1772

  • DOI: https://doi.org/10.1016/j.bmcl.2011.01.065
  • Primary Citation of Related Structures:  
    3APC, 3APD, 3APF

  • PubMed Abstract: 

    Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase and a promising therapeutic target for cancer. Using structure-based drug design (SBDD), we have identified novel PI3K inhibitors with a dihydropyrrolopyrimidine skeleton. Metabolic stability of the first lead series was drastically improved by replacing phenol with aminopyrimidine moiety. CH5132799, a novel class I PI3K inhibitor, exhibited a strong inhibitory activity especially against PI3Kα (IC(50)=0.014 μM). In human tumor cell lines with PI3K pathway activation, CH5132799 showed potent antiproliferative activity. CH5132799 is orally available and showed significant antitumor activity in PI3K pathway-activated human cancer xenograft models in mice.

    • Organizational Affiliation: 

    Research Division, Chugai Pharmaceutical Co., Ltd , Kamakura, Kanagawa, Japan. ohwadajn@chugai-pharm.co.jp


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): 0 
Gene Names: PIK3CG
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MMD
Query on MMD
Download Ideal Coordinates CCD File 
B [auth A]5-(7-Methanesulfonyl-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-ylamine
C15 H19 N7 O3 S
JEGHXKRHKHPBJD-UHFFFAOYSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
MMD PDBBind:  3APC IC50: 36 (nM) from 1 assay(s)
BindingDB:  3APC IC50: 36 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.54 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.239 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 142.91α = 90
b = 67.55β = 95.74
c = 106.49γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
XDSdata reduction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description