MedKoo Cat#: 329486 | Name: Aprocitentan
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Description:

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

Aprocitentan, also known as ACT-132577, is an endothelin receptor antagonist and an pharmacologically active metabolite of macitentan (MedKoo Cat#205912). Aprocitentan antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range.

Chemical Structure

Aprocitentan
CAS#1103522-45-7

Theoretical Analysis

MedKoo Cat#: 329486

Name: Aprocitentan

CAS#: 1103522-45-7

Chemical Formula: C16H14Br2N6O4S

Exact Mass: 543.9164

Molecular Weight: 546.19

Elemental Analysis: C, 35.18; H, 2.58; Br, 29.26; N, 15.39; O, 11.72; S, 5.87

Price and Availability

Size Price Availability Quantity
25mg USD 750.00 2 Weeks
100mg USD 1,950.00 2 Weeks
1g USD 3,650.00 2 Weeks
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Synonym
Aprocitentan; ACT-132577; ACT 132577; ACT132577; Despropyl Macitentan.
IUPAC/Chemical Name
N-[5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl]sulfuric diamide
InChi Key
DKULOVKANLVDEA-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H14Br2N6O4S/c17-11-3-1-10(2-4-11)13-14(24-29(19,25)26)22-9-23-15(13)27-5-6-28-16-20-7-12(18)8-21-16/h1-4,7-9H,5-6H2,(H2,19,25,26)(H,22,23,24)
SMILES Code
O=S(NC1=NC=NC(OCCOC2=NC=C(Br)C=N2)=C1C3=CC=C(Br)C=C3)(N)=O
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
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

Preparing Stock Solutions

The following data is based on the product molecular weight 546.19 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.

Recalculate based on batch purity %
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
1: Schlaich MP, Bellet M, Weber MA, Danaietash P, Bakris GL, Flack JM, Dreier RF, Sassi-Sayadi M, Haskell LP, Narkiewicz K, Wang JG; PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. Lancet. 2022 Dec 3;400(10367):1927-1937. doi: 10.1016/S0140-6736(22)02034-7. Epub 2022 Nov 7. Erratum in: Lancet. 2023 Jan 28;401(10373):268. PMID: 36356632. 2: Varzideh F, Kansakar U, Jankauskas SS, Santulli G. Aprocitentan: New insights. Front Cardiovasc Med. 2022 Dec 22;9:1093406. doi: 10.3389/fcvm.2022.1093406. PMID: 36620614; PMCID: PMC9813740. 3: Danaietash P, Verweij P, Wang JG, Dresser G, Kantola I, Lawrence MK, Narkiewicz K, Schlaich M, Bellet M; PRECISION investigators. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertens (Greenwich). 2022 Jul;24(7):804-813. doi: 10.1111/jch.14517. Epub 2022 Jun 9. PMID: 35686330; PMCID: PMC9278594. 4: Clozel M. Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol. 2022 Jul 1;100(7):573-583. doi: 10.1139/cjpp-2022-0010. Epub 2022 Apr 3. PMID: 35245103. 5: Angeli F, Verdecchia P, Reboldi G. Aprocitentan, A Dual Endothelin Receptor Antagonist Under Development for the Treatment of Resistant Hypertension. Cardiol Ther. 2021 Dec;10(2):397-406. doi: 10.1007/s40119-021-00233-7. Epub 2021 Jul 12. PMID: 34251649; PMCID: PMC8555037. 6: McCoy EK, Lisenby KM. Aprocitentan (a Dual Endothelin-Receptor Antagonist) for Treatment-Resistant Hypertension. J Cardiovasc Pharmacol. 2021 Jun 1;77(6):699-706. doi: 10.1097/FJC.0000000000001023. PMID: 34001723. 7: Sidharta PN, Dingemanse J. Effects of Multiple-Dose Administration of Aprocitentan on the Pharmacokinetics of Rosuvastatin. Clin Pharmacol Drug Dev. 2020 Nov;9(8):995-1002. doi: 10.1002/cpdd.815. Epub 2020 Jun 27. PMID: 32592633. 8: Sidharta PN, Dingemanse J. Effect of Multiple-Dose Aprocitentan Administration on the Pharmacokinetics of Midazolam in Healthy Male Subjects. Eur J Drug Metab Pharmacokinet. 2020 Apr;45(2):227-234. doi: 10.1007/s13318-019-00590-8. PMID: 31773427. 9: Mahfooz K, Najeed S, Tun HN, Khamosh M, Grewal D, Hussain A, Ong K, Dharmarajan L, Vasavada A. New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension: A Systematic Review and Meta-Analysis. Curr Probl Cardiol. 2023 Jul;48(7):101686. doi: 10.1016/j.cpcardiol.2023.101686. Epub 2023 Mar 8. PMID: 36893968. 10: Höcht C, Allo MA, Polizio AH, Morettón MA, Carranza A, Chiappetta DA, Choi MR. New and developing pharmacotherapies for hypertension. Expert Rev Cardiovasc Ther. 2022 Aug;20(8):647-666. doi: 10.1080/14779072.2022.2105204. Epub 2022 Aug 3. PMID: 35880547. 11: Sidharta PN, Fischer H, Dingemanse J. Absorption, Distribution, Metabolism, and Excretion of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Humans. Curr Drug Metab. 2021;22(5):399-410. doi: 10.2174/1389200222666210204202815. PMID: 33563190. 12: Verweij P, Danaietash P, Flamion B, Ménard J, Bellet M. Randomized Dose- Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension. Hypertension. 2020 Apr;75(4):956-965. doi: 10.1161/HYPERTENSIONAHA.119.14504. Epub 2020 Feb 17. PMID: 32063059; PMCID: PMC7098434. 13: Fontes MSC, Dingemanse J, Halabi A, Tomaszewska-Kiecana M, Sidharta PN. Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment. Sci Rep. 2022 Nov 9;12(1):19067. doi: 10.1038/s41598-022-22470-z. PMID: 36352054; PMCID: PMC9645340. 14: Trensz F, Bortolamiol C, Kramberg M, Wanner D, Hadana H, Rey M, Strasser DS, Delahaye S, Hess P, Vezzali E, Mentzel U, Ménard J, Clozel M, Iglarz M. Pharmacological Characterization of Aprocitentan, a Dual Endothelin Receptor Antagonist, Alone and in Combination with Blockers of the Renin Angiotensin System, in Two Models of Experimental Hypertension. J Pharmacol Exp Ther. 2019 Mar;368(3):462-473. doi: 10.1124/jpet.118.253864. Epub 2019 Jan 8. PMID: 30622171. 15: Fontes MSC, Dingemanse J, Sidharta PN. Multiple-Dose Pharmacokinetics, Safety, and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Healthy Japanese and Caucasian Subjects. Clin Pharmacol Drug Dev. 2021 Jul;10(7):718-725. doi: 10.1002/cpdd.881. Epub 2020 Oct 15. PMID: 33063477. 16: Gueneau de Mussy P, Sidharta PN, Wuerzner G, Maillard MP, Guérard N, Iglarz M, Flamion B, Dingemanse J, Burnier M. Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet. Clin Pharmacol Ther. 2021 Mar;109(3):746-753. doi: 10.1002/cpt.2043. Epub 2020 Sep 29. PMID: 32897570; PMCID: PMC7984323. 17: Bartolucci R, Dosne AG, Csonka D, Pérez-Ruixo JJ, Magni P, Poggesi I. A Population Pharmacokinetic Model of Macitentan and Its Active Metabolite Aprocitentan in Healthy Volunteers and Patients with Pulmonary Arterial Hypertension. Clin Pharmacokinet. 2021 Dec;60(12):1605-1619. doi: 10.1007/s40262-021-01049-3. Epub 2021 Jun 23. PMID: 34159557. 18: Sidharta PN, Ulč I, Dingemanse J. Single-Dose Pharmacokinetics and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Subjects with Severe Renal Function Impairment. Clin Drug Investig. 2019 Nov;39(11):1117-1123. doi: 10.1007/s40261-019-00837-x. PMID: 31435905. 19: Sidharta PN, Melchior M, Kankam MK, Dingemanse J. Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjects. Drug Des Devel Ther. 2019 Mar 22;13:949-964. doi: 10.2147/DDDT.S199051. PMID: 30962677; PMCID: PMC6435120. 20: Boutari C, Siskos F. Novel Dual Endothelin Inhibitors in the Management of Resistant Hypertension. Life (Basel). 2023 Mar 16;13(3):806. doi: 10.3390/life13030806. PMID: 36983961; PMCID: PMC10051756.