Atopaxar | E5555 | CAS#751475-53-3 | PAR-1 inhibitor

MedKoo Cat#: 319757 | Name: Atopaxar

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Atopaxar, also known as E5555, is a potent and orally-active PAR-1 inhibitor. E5555 inhibited the binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP) to PAR-1 with a half maximal inhibitory concentration (IC(50)) value of 0.019μM. E5555 showed potent inhibitory effects on human platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.064 and 0.031μM, respectively. E5555 showed potent and selective inhibitory effects on guinea pig platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.13 and 0.097μM, respectively. E5555 could be a therapeutic option for atherothrombotic disease.

Chemical Structure

Atopaxar

CAS#751475-53-3 (free base)

Theoretical Analysis

MedKoo Cat#: 319757

Name: Atopaxar

CAS#: 751475-53-3 (free base)

Chemical Formula: C29H38FN3O5

Exact Mass: 527.2795

Molecular Weight: 527.64

Elemental Analysis: C, 66.01; H, 7.26; F, 3.60; N, 7.96; O, 15.16

Price and Availability

Size	Price	Availability
100mg	USD 1,850.00	2 Weeks
200mg	USD 2,850.00	2 Weeks
500mg	USD 3,450.00	2 Weeks
1g	USD 4,850.00	2 Weeks
2g	USD 7,450.00	2 Weeks

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Related CAS #

751475-53-3 (free base) 474550-69-1 (HBr) 474544-83-7 (HCl)

Synonym

E5555; E-5555; E 5555; ER-172594-00; ER172594-00; ER 172594-00; Atopaxar

IUPAC/Chemical Name

1-(3-(tert-butyl)-4-methoxy-5-morpholinophenyl)-2-(5,6-diethoxy-7-fluoro-1-iminoisoindolin-2-yl)ethan-1-one

InChi Key

QWKAUGRRIXBIPO-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H38FN3O5/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

SMILES Code

COC1=C(N2CCOCC2)C=C(C(CN(CC3=C4C(F)=C(OCC)C(OCC)=C3)C4=N)=O)C=C1C(C)(C)C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 527.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

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Invest New Drugs. 2020 Aug;38(4):1003-1011. doi: 10.1007/s10637-019-00853-w. Epub 2019 Oct 14. PMID: 31612426. 5: Wurster T, May AE. Atopaxar. A novel player in antiplatelet therapy? Hamostaseologie. 2012;32(3):228-33. doi: 10.5482/HAMO-12-05-0009. PMID: 22859265. 6: Wiviott SD, Flather MD, O'Donoghue ML, Goto S, Fitzgerald DJ, Cura F, Aylward P, Guetta V, Dudek D, Contant CF, Angiolillo DJ, Bhatt DL; LANCELOT-CAD Investigators. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin–Coronary Artery Disease Trial. Circulation. 2011 May 3;123(17):1854-63. doi: 10.1161/CIRCULATIONAHA.110.001404. Epub 2011 Apr 18. PMID: 21502571. 7: O'Donoghue ML, Bhatt DL, Wiviott SD, Goodman SG, Fitzgerald DJ, Angiolillo DJ, Goto S, Montalescot G, Zeymer U, Aylward PE, Guetta V, Dudek D, Ziecina R, Contant CF, Flather MD; LANCELOT-ACS Investigators. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin–Acute Coronary Syndromes Trial. Circulation. 2011 May 3;123(17):1843-53. doi: 10.1161/CIRCULATIONAHA.110.000786. Epub 2011 Apr 18. PMID: 21502577. 8: Pan H, Boucher M, Kaunelis D. PAR-1 Antagonists: An Emerging Antiplatelet Drug Class. 2016 Sep 30. In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016–. 148. PMID: 27809429. 9: Olivier C, Diehl P, Bode C, Moser M. Thrombin receptor antagonism in antiplatelet therapy. Cardiol Ther. 2013 Jun;2(1):57-68. doi: 10.1007/s40119-013-0013-4. Epub 2013 Mar 7. PMID: 25135289; PMCID: PMC4107434. 10: Gao L, Zhao FL, Li SC. Efficacy and Safety of Thrombin-Receptor Antagonist (Atopaxar and Vorapaxar) in Patients with Acute Coronary Syndrome or Coronary Artery Disease-A Meta-Analysis of Randomized Controlled Trials. Value Health Reg Issues. 2015 May;6:22-32. doi: 10.1016/j.vhri.2015.01.003. Epub 2015 May 16. PMID: 29698189. 11: Al-Khafaji K, Mutyala M, Al-Khafaji N, Harper Y, Ismail I, Hakim H, Arora RR. Protease-Activated Receptor 1 Inhibitors: Novel Antiplatelet Drugs in Prevention of Atherothrombosis. Am J Ther. 2017 Nov/Dec;24(6):e730-e736. doi: 10.1097/MJT.0000000000000347. PMID: 26398717. 12: Zhou P, Yin JX, Tao HL, Zhang HW. Pathogenesis and management of heparin- induced thrombocytopenia and thrombosis. Clin Chim Acta. 2020 May;504:73-80. doi: 10.1016/j.cca.2020.02.002. Epub 2020 Feb 4. PMID: 32032610. 13: Kogushi M, Matsuoka T, Kuramochi H, Murakami K, Kawata T, Kimura A, Chiba K, Musha T, Suzuki S, Kawahara T, Kajiwara A, Hishinuma I. Oral administration of the thrombin receptor antagonist E5555 (atopaxar) attenuates intimal thickening following balloon injury in rats. Eur J Pharmacol. 2011 Sep;666(1-3):158-64. doi: 10.1016/j.ejphar.2011.05.034. Epub 2011 May 27. PMID: 21635884. 14: Klonaris C, Patelis N, Drebes A, Matheiken S, Liakakos T. Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents. Curr Pharm Des. 2016;22(29):4610-4616. doi: 10.2174/1381612822666160607065109. PMID: 27281329. 15: Chatterjee S, Sharma A, Mukherjee D. PAR-1 antagonists: current state of evidence. J Thromb Thrombolysis. 2013 Jan;35(1):1-9. doi: 10.1007/s11239-012-0752-4. PMID: 22644721. 16: Gurbel PA, Jeong YH, Tantry US. Vorapaxar: a novel protease-activated receptor-1 inhibitor. Expert Opin Investig Drugs. 2011 Oct;20(10):1445-53. doi: 10.1517/13543784.2011.606809. Epub 2011 Aug 6. PMID: 21819272. 17: Niespialowska-Steuden M, Collins P, Costopoulos C, Gorog DA. NOAC in acute coronary syndrome and AF? Cardiovasc Hematol Disord Drug Targets. 2014;14(2):154-64. doi: 10.2174/1871529x14666140701100338. Erratum in: Cardiovasc Hematol Disord Drug Targets. 2015;15(1):85. PMID: 24993123. 18: Goto S, Ogawa H, Takeuchi M, Flather MD, Bhatt DL; J-LANCELOT (Japanese- Lesson from Antagonizing the Cellular Effect of Thrombin) Investigators. 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. Eur Heart J. 2010 Nov;31(21):2601-13. doi: 10.1093/eurheartj/ehq320. Epub 2010 Aug 30. PMID: 20805115; PMCID: PMC2966970. 19: Ji X, Hou M. Novel agents for anti-platelet therapy. J Hematol Oncol. 2011 Nov 4;4:44. doi: 10.1186/1756-8722-4-44. PMID: 22053759; PMCID: PMC3224753. 20: Kogushi M, Matsuoka T, Kawata T, Kuramochi H, Kawaguchi S, Murakami K, Hiyoshi H, Suzuki S, Kawahara T, Kajiwara A, Hishinuma I. The novel and orally active thrombin receptor antagonist E5555 (Atopaxar) inhibits arterial thrombosis without affecting bleeding time in guinea pigs. Eur J Pharmacol. 2011 Apr 25;657(1-3):131-7. doi: 10.1016/j.ejphar.2011.01.058. Epub 2011 Feb 4. PMID: 21300059.