3R7R

Structure-based design of thienobenzoxepin inhibitors of PI3-Kinase

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Structure-based design of thienobenzoxepin inhibitors of PI3-kinase.

Staben, S.T., Siu, M., Goldsmith, R., Olivero, A.G., Do, S., Burdick, D.J., Heffron, T.P., Dotson, J., Sutherlin, D.P., Zhu, B.Y., Tsui, V., Le, H., Lee, L., Lesnick, J., Lewis, C., Murray, J.M., Nonomiya, J., Pang, J., Prior, W.W., Salphati, L., Rouge, L., Sampath, D., Sideris, S., Wiesmann, C., Wu, P.

(2011) Bioorg Med Chem Lett 21: 4054-4058

  • DOI: https://doi.org/10.1016/j.bmcl.2011.04.124
  • Primary Citation of Related Structures:  
    3R7Q, 3R7R

  • PubMed Abstract: 

    Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenograft model.

    • Organizational Affiliation: 

    Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. stevents@gene.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): 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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAZ
Query on FAZ
Download Ideal Coordinates CCD File 
B [auth A]8-(acetylamino)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxamide
C22 H19 Cl N2 O3 S
RTUHEKLMDKJAQG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FAZ PDBBind:  3R7R IC50: 1.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.792α = 90
b = 67.868β = 95.4
c = 106.933γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction

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: 2011-08-03
    Type: Initial release
  • Version 1.1: 2012-09-05
    Changes: Database references
  • Version 1.2: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description