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E5700 as squalene synthase inhibitor

SUBMISSION ID 427

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

TitleE5700 as squalene synthase inhibitor
Executive Summary/Abstract Through the exploratory research for treatment of hypolipidemia, E5700 was found to be a novel squalene synthase inhibitor, E5700 possesses potent squalene synthase inhibitory activity and shows inhibitory activity to hepatic cholesterol biosynthesis in rats. It is also reported that E5700 possesses some activities against Leishmania amazonensis, Toxoplasma gondii tachyzoites, and Trypanosoma cruzi.
Keywords Toxoplasma; squalene; Trypanosoma; Leishmania; synthase

Disease Selection

Disease Chagas disease (American trypanosomiasis);Leishmaniasis
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_E5700.pdf
SAR analysis summary
Scale-up synthesis route

Pre-Clinical Candidate Profile

 
Potency
Off-target Activity
Animal Model/Data Description 1 IC50 for squalene synthase in liver microsomes isolated from human=0.332 nM 2 ED50 for hepatic cholesterol biosynthesis in rats inhibited=0.52 mg/kg. 3 Low nanomolar IC50 range for antiproliferative effects against promastigotes and intracellular amastigotes of Leishmania amazonensis Josefaa 4 IC50 for anti-Toxoplasma gondii arresting parasite growth =0.23 micro M 5 Dose dependent effect on parasitemia and survival in murine model of acute Chagas disease.
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

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) Antimicrobial Agent Chemotherapy. 2004, p. 2379–2387.; J. Antimicrobial Chemotherapy. 2006, 58, 59–65.; Antimicrobial Agent Chemotherapy. 2008, 4098–4114.
Patented Data (Reference)