3TGG

A novel series of potent and selective PDE5 inhibitor2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Investigation of the pyrazinones as PDE5 inhibitors: evaluation of regioisomeric projections into the solvent region.

Hughes, R.O.Maddux, T.Joseph Rogier, D.Lu, S.Walker, J.K.Jon Jacobsen, E.Rumsey, J.M.Zheng, Y.Macinnes, A.Bond, B.R.Han, S.

(2011) Bioorg Med Chem Lett 21: 6348-6352

  • DOI: https://doi.org/10.1016/j.bmcl.2011.08.106
  • Primary Citation of Related Structures:  
    3TGE, 3TGG

  • PubMed Abstract: 

    We describe the design, synthesis and profiling of a novel series of PDE5 inhibitors. We take advantage of an alternate projection into the solvent region to identify compounds with excellent potency, selectivity and pharmacokinetic profiles.


  • Organizational Affiliation

    Pfizer Global Research and Development, 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. robowenhughes@gmail.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cGMP-specific 3',5'-cyclic phosphodiesterase326Homo sapiensMutation(s): 13 
Gene Names: PDE5APDE5
EC: 3.1.4.35
UniProt & NIH Common Fund Data Resources
Find proteins for O76074 (Homo sapiens)
Explore O76074 
Go to UniProtKB:  O76074
PHAROS:  O76074
GTEx:  ENSG00000138735 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO76074
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0H3
Query on 0H3

Download Ideal Coordinates CCD File 
D [auth A]7-(6-methoxypyridin-3-yl)-4-{[2-(propan-2-yloxy)ethyl]amino}-1-(2-propoxyethyl)pyrido[4,3-d]pyrimidin-2(1H)-one
C23 H31 N5 O4
WVANLBXFBJNOKP-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0H3 BindingDB:  3TGG IC50: 0.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.493α = 90
b = 76.508β = 102.42
c = 76.811γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2012-01-25 
  • Deposition Author(s): Han, S.

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-25
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations