5G3N

Discovery of a novel secreted phospholipase A2 (sPLA2) inhibitor.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of Azd2716: A Novel Secreted Phospholipase A2 (Spla2) Inhibitor for the Treatment of Coronary Artery Disease

Giordanetto, F.Pettersen, D.Starke, I.Nordberg, P.Dahlstrom, M.Knerr, L.Selmi, N.Rosengren, B.Larsson, L.O.Sandmark, J.Castaldo, M.Dekker, N.Karlsson, U.Hurt-Camejo, E.

(2016) ACS Med Chem Lett 7: 884

  • DOI: https://doi.org/10.1021/acsmedchemlett.6b00188
  • Primary Citation of Related Structures:  
    5G3M, 5G3N

  • PubMed Abstract: 

    Expedited structure-based optimization of the initial fragment hit 1 led to the design of ( R )- 7 (AZD2716) a novel, potent secreted phospholipase A 2 (sPLA 2 ) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, ( R )- 7 was selected as a clinical candidate for the treatment of coronary artery disease.


  • Organizational Affiliation

    Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PHOSPHOLIPASE A2, MEMBRANE ASSOCIATED
A, B
127Homo sapiensMutation(s): 2 
EC: 3.1.1.4
UniProt & NIH Common Fund Data Resources
Find proteins for P14555 (Homo sapiens)
Explore P14555 
Go to UniProtKB:  P14555
PHAROS:  P14555
GTEx:  ENSG00000188257 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14555
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
X28
Query on X28

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B]
3-(5'-BENZYL-2'-CARBAMOYLBIPHENYL-3-YL)PROPANOIC ACID
C23 H21 N O3
UHEGDWIZAOPGIY-UHFFFAOYSA-N
FMT
Query on FMT

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
G [auth B],
H [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
X28 Binding MOAD:  5G3N IC50: 12 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.1α = 90
b = 66.53β = 90
c = 73.77γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
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: 2016-09-14
    Type: Initial release
  • Version 1.1: 2016-11-09
    Changes: Database references
  • Version 1.2: 2018-04-04
    Changes: Data collection