Re:Search - Details

E4021 as type V phosphodiesterase (PDE) inhibitor

SUBMISSION ID 443

Contact Details

Provider Eisai Co., Ltd. - Eisai
Partnership Hub Coordinator Name BIO Ventures for Global Health
401 Terry Avenue North
Seattle, WA 98109
USA
Tel: +1 206 732 2122
info@bvgh.org

Submission Summary

TitleE4021 as type V phosphodiesterase (PDE) inhibitor
Executive Summary/Abstract E4021 is selective type V PDE inhibitor. E4021 caused a significant and sustained increase in the cGMP level in endothelium-denuded porcine coronary artery without effecting the cAMP level. E4021 had a relaxant effect in porcine coronary artery precontracted by prostaglandin F2, in the absence of endothelial cells and relaxed it more markedly in the presence of endothelial cells. E4021 caused a dose-dependent dilation of the large epicardial coronary artery, with a reduction in mean pulmonary arterial pressure, in conscious pigs instrumented chronically with a pair of piezoelectric crystals. E4021 causes relaxation of the large coronary artery via an increase in the cGMP level.
Keywords Phosphodiesterase, PDE5, hypertension

Disease Selection

Disease Unknown
Comment
Name(s) of Infectious Organism(s)
Vector(s)
Human Target Organ(s)
Mechanism of Action (MoA)
Molecular or Cellular Target Name(s)

Type of Data

Type of Data Pre-Clinical Candidate










PRE-CLINICAL CANDIDATE DATA SUBFIELDS

Pre-Clinical Candidate Description

 
Strategy for selecting Pre-Clinical Candidate
Origin of Pre-Clinical Lead and Lead Series
How many Pre-Clinical Candidates have been Selected?
How many Pre-Clinical Candidates Abandoned?
Reason for Abandoning
How many Pre-Clinical Candidates Untouched?
Reason for Not Pursuing

Pre-Clinical Chemistry Description

 
Chemistry approach(es) to Pre-Clinical Candidate
Chemical structure(s) of Pre-Clinical Candidate
C125_E4021.pdf
SAR analysis summary
Scale-up synthesis route

Pre-Clinical Candidate Profile

 
Potency
Off-target Activity
Animal Model/Data Description 1 IC50 for type V PDE from porcine aorta = 0.0039 micro M 2 EC50 for vasorelaxant in PGF2a-contracted porcine coronary artery preparation with endotheliun = 0.11 micro M. 3 In conscious pigs, E4021 does-dependently dilated the large coronary artery but had no effect on coronary flow velocity in vivo .
In Vitro & In Vivo PK/PD
Solubility
Non-GMP/GMP Animal Tox and DMPK Data Summary
Safety Summary
Formulation
Other

Pre-Clinical Compound Availability

 
Quantity Produced in grams
Quantity Available in grams 0.01

Mechanism of Action (MoA)

 
Is the Mechanism of Action Known? No

Collaboration Status

 
In house only Yes

Publication/Patent Status

 
Proprietary Data Yes
Publicly Available Data (Reference) Jpn. J. Pharmacol., 77, 99-102, 1998.; J. Pharmacol. Exp. Ther., 272, 825-831, 1995.
Patented Data (Reference)