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Details

Stereochemistry ACHIRAL
Molecular Formula C29H38FN3O5.ClH
Molecular Weight 564.088
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ATOPAXAR HYDROCHLORIDE

SMILES

Cl.CCOC1=CC2=C(C(=N)N(CC(=O)C3=CC(N4CCOCC4)=C(OC)C(=C3)C(C)(C)C)C2)C(F)=C1OCC

InChI

InChIKey=DUUYZYAKJMJYJV-UHFFFAOYSA-N
InChI=1S/C29H38FN3O5.ClH/c1-7-37-23-15-19-16-33(28(31)24(19)25(30)27(23)38-8-2)17-22(34)18-13-20(29(3,4)5)26(35-6)21(14-18)32-9-11-36-12-10-32;/h13-15,31H,7-12,16-17H2,1-6H3;1H

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C29H38FN3O5
Molecular Weight 527.6275
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22871190 | https://www.ncbi.nlm.nih.gov/pubmed/25135289 |https://www.ncbi.nlm.nih.gov/pubmed/21300059

Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor-1 (PAR-1) thrombin receptor antagonist. The inhibition of thrombin-mediated platelet activation by means of protease-activated receptor-1 inhibitors represents an attractive therapeutic option for patients with atherothrombotic disease processes. In preclinical studies, atopaxar demonstrated inhibition of thrombin receptor-activating peptides (TRAP)- and thrombin-induced platelet aggregation. Atopaxar was being developed by Eisai for acute coronary syndromes (ACS) and coronary disorders, including atherothrombosis, unstable angina pectoris and myocardial infarction. Atopaxar was in phase II clinical development in the US, EU and Japan. However, development was discontinued in May 2012.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 19.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502571
Page: p.1858
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: coronary artery disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502571
Page: p.1858
Disc. AE: Bleeding...
AEs leading to
discontinuation/dose reduction:
Bleeding (1.61%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502571
Page: p.1858
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502577
Page: p.1848
unhealthy, ADULT
n = 148
Health Status: unhealthy
Condition: coronary artery disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 148
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502577
Page: p.1848
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502577
Page: p.1848
AEs

AEs

AESignificanceDosePopulation
Bleeding 1.61%
Disc. AE
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502571
Page: p.1858
unhealthy, ADULT
n = 186
Health Status: unhealthy
Condition: coronary artery disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 186
Sources:
https://pubmed.ncbi.nlm.nih.gov/21502571
Page: p.1858
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 inconclusive [IC50 18.3564 uM]
CYP2D6
1891
 yes [IC50 5.3547 uM]
CYP2C9
1819
 yes [IC50 6.0081 uM]
CYP3A4
1925
 yes [IC50 7.5637 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
PubMed

PubMed

TitleDatePubMed
The in-vitro effects of E5555, a protease-activated receptor (PAR)-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease.
2009 Jul
Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease.
2010 Nov
The novel and orally active thrombin receptor antagonist E5555 (Atopaxar) inhibits arterial thrombosis without affecting bleeding time in guinea pigs.
2011 Apr 25
Atopaxar: a review of its mechanism of action and role in patients with coronary artery disease.
2012 Jul
Patents

Patents

20050004204
3
WO/2015/090705A1
3
WO/2016/066789A1
3
WO/2016/066789A4
3

Sample Use Guides

In Vivo Use Guide
In phase 2 study : Patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD) received Atopaxar (E5555) (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition.
Route of Administration: Oral
In Vitro Use Guide
Platelet inhibition was usually moderate, present already at 20 ng/ml of Atopaxar (E5555), and was not seemingly dose-dependent without TRAP stimulation. E5555 caused 10-15% inhibition of ADP- and collagen-induced platelet aggregation in plasma, but not in whole blood. TRAP-induced aggregation was inhibited almost completely. PECAM-I, GP IIb/IIIa antigen, and activity with PAC-1, GPIb, thrombospondin, vitronectin receptor expression, and formation of platelet-monocyte aggregates were also significantly reduced by E5555. TRAP stimulation caused dose-dependent effects between 20 and 50 ng/ml E5555 doses.
Substance Class Chemical
Created
by admin
on Sat Dec 16 05:32:12 GMT 2023
Edited
by admin
on Sat Dec 16 05:32:12 GMT 2023
Record UNII
8J718S3ET9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ATOPAXAR HYDROCHLORIDE
USAN  
USAN  
Official Name English
ATOPAXAR HYDROCHLORIDE [USAN]
Common Name English
ETHANONE, 2-(5,6-DIETHOXY-7-FLUORO-1,3-DIHYDRO-1-IMINO-2H-ISOINDOL-2-YL)-1-(3-(1,1-DIMETHYLETHYL)-4-METHOXY-5-(4-MORPHOLINYL)PHENYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1327
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
Code System Code Type Description
PUBCHEM
67136661
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
PRIMARY
DRUG BANK
DBSALT002127
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
PRIMARY
NCI_THESAURUS
C142938
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
PRIMARY
FDA UNII
8J718S3ET9
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
PRIMARY
CAS
474544-83-7
Created by admin on Sat Dec 16 05:32:12 GMT 2023 , Edited by admin on Sat Dec 16 05:32:12 GMT 2023
PRIMARY
Related Record Type Details
Structure of ATOPAXAR
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of ATOPAXAR
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