Macitentan

• CAT Number: A000156
• CAS Number: 441798-33-0
• Molecular Formula: C19H20Br2N6O4S
• Molecular Weight: 588.27
• Purity: ≥95%
• Target: Endothelin Receptor
• Solubility: >21.2mg/mL in DMSO
• Storage: 3 years, -20°C
• IUPAC Name: 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-N-(propylsulfamoyl)pyrimidin-4-amine
• InChI: InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)
• InChIKey: JGCMEBMXRHSZKX-UHFFFAOYSA-N
• SMILES: CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br

Macitentan (trade name Opsumit) (CAS 441798-33-0) is an endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype. The drug received approval from the U.S. Food and Drug Administration (FDA) on October 13, 2013.

Overview of Clinical Research

Macitentan is an endothelin A receptor antagonist and endothelin B receptor antagonist developed by Actelion Pharmaceuticals. 

Reference

1: Nadeau V, Potus F, Boucherat O, Paradis R, Tremblay E, Iglarz M, Paulin R, Bonnet S, Provencher S. EXPRESS: Dual et(a)/et(b) blockade with macitentan improves both vascular remodelling and angiogenesis in pulmonary arterial hypertension. Pulm Circ. 2017 Jan 1:2045893217741429. doi: 10.1177/2045893217741429. [Epub ahead of print] PubMed PMID: 29064353.
2: Correale M, Tarantino N, Paradiso G, Monaco I, Di Biase M, Brunetti ND. Macitentan Use in a Neurofibromatosis Type 1 Patient With Pulmonary Hypertension and External Jugular Phlebectasia. Am J Ther. 2017 Oct 20. doi: 10.1097/MJT.0000000000000601. [Epub ahead of print] PubMed PMID: 29059078.
3: Ghofrani HA, Simonneau G, D/'Armini AM, Fedullo P, Howard LS, Jaïs X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11. PubMed PMID: 28919201.
4: Torbicki A. Macitentan for treatment of CTEPH: why MERIT merits attention. Lancet Respir Med. 2017 Oct;5(10):762-763. doi: 10.1016/S2213-2600(17)30342-9. Epub 2017 Sep 11. PubMed PMID: 28919198.
5: Wacker J, Weintraub RG. Macitentan in Pulmonary Arterial Hypertension Associated with Congenital Heart Defects. Heart Lung Circ. 2017 Oct;26(10):1006-1007. doi: 10.1016/j.hlc.2017.08.003. PubMed PMID: 28867027.
6: Bolli MH. The Discovery of Macitentan – A Standard Medicinal Chemistry Program? Chimia (Aarau). 2017 Aug 9;71(7):420-429. doi: 10.2533/chimia.2016.420. PubMed PMID: 28779766.
7: Rahaghi FF, Alnuaimat HM, Awdish RLA, Balasubramanian VP, Bourge RC, Burger CD, Butler J, Cauthen CG, Chakinala MM, deBoisblanc BP, Eggert MS, Engel P, Feldman J, McConnell JW, Park M, Sager JS, Sood N, Palevsky HI. Recommendations for the clinical management of patients receiving macitentan for pulmonary arterial hypertension (PAH): A Delphi consensus document. Pulm Circ. 2017 Jul-Sep;7(3):702-711. doi: 10.1177/2045893217721695. Epub 2017 Aug 22. PubMed PMID: 28671484.
8: Demetriades P, Aziz A, Condliffe R, Bowater SE, Clift PF. The use of Macitentan in Fontan circulation: a case report. BMC Cardiovasc Disord. 2017 May 22;17(1):131. doi: 10.1186/s12872-017-0567-5. PubMed PMID: 28532389; PubMed Central PMCID: PMC5440995.
9: Issac M, Dingemanse J, Sidharta PN. Pharmacokinetics of Macitentan in Patients With Pulmonary Arterial Hypertension and Comparison With Healthy Subjects. J Clin Pharmacol. 2017 Aug;57(8):997-1004. doi: 10.1002/jcph.888. Epub 2017 Apr 5. PubMed PMID: 28378883.
10: Moiseeva OM, Rudakova AV. [Pharmacoeconomic aspects of macitentan in the therapy of pulmonary arterial hypertension]. Ter Arkh. 2017;89(3):72-77. doi: 10.17116/terarkh201789372-77. Russian. PubMed PMID: 28378734.