| 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
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
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| 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 |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
PubMed
Sample Use Guides
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
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.
