3TGE

A novel series of potent and selective PDE5 inhibitor1

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 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): 0 
Gene Names: PDE5A, PDE5
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
TGE
Query on TGE
Download Ideal Coordinates CCD File 
D [auth A]7-(6-methoxypyridin-3-yl)-3-{[2-(morpholin-4-yl)ethyl]amino}-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
C24 H32 N6 O4
OFRWMWHKNKWEHT-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
TGE PDBBind:  3TGE IC50: 0.07 (nM) from 1 assay(s)
BindingDB:  3TGE IC50: 0.07 (nM) from 1 assay(s)
Binding MOAD:  3TGE IC50: 0.07 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.63α = 90
b = 77.311β = 101.19
c = 78.265γ = 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 


View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2011-11-09 
    • Deposition Author(s): Han, S.

Revision History  (Full details and data files)

  • Version 1.0: 2011-11-09
    Type: Initial release
  • Version 1.1: 2017-08-16
    Changes: Refinement description, Source and taxonomy
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations