Aprocitentan

Aprocitentan, sold under the brand name Tryvio, is a medication used to treat hypertension (high blood pressure).^[1] It is developed by Idorsia.^[4] It is taken by mouth.^[1]

Aprocitentan

Clinical data
Trade names	Tryvio
Other names	ACT-132577
AHFS/Drugs.com	Monograph
Routes of administration	By mouth
Drug class	Antihypertensive
ATC code	C02KN01 (WHO)
Legal status
Legal status	US: ℞-only[1] EU: Rx-only[2][3]
Identifiers
IUPAC name 5-(4-Bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine
CAS Number	1103522-45-7
PubChem CID	25099191
IUPHAR/BPS	10070
DrugBank	DB15059
ChemSpider	25027753
UNII	MZI81HV01P
KEGG	D11441
ChEBI	CHEBI:76609
ChEMBL	ChEMBL2165326
Chemical and physical data
Formula	C16H14Br2N6O4S
Molar mass	546.19 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC(=CC=C1C2=C(N=CN=C2OCCOC3=NC=C(C=N3)Br)NS(=O)(=O)N)Br
InChI 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) Key:DKULOVKANLVDEA-UHFFFAOYSA-N

Aprocitentan is a receptor antagonist that targets both endothelin A and endothelin B receptors.^[5][6]

Aprocitentan was approved for medical use in the United States in March 2024.^[1][4][7] It is the first endothelin receptor antagonist to be approved by the US Food and Drug Administration (FDA) to treat systemic hypertension.^[4] The FDA considers it to be a first-in-class medication.^[8]

Medical uses

Aprocitentan is indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adults who are not adequately controlled on other medications.^[1]

Adverse effects

Aprocitentan may cause hepatotoxicity (liver damage), edema (fluid retention), anemia (reduced hemoglobin), and decreased sperm count.^[1]

Contraindications

Data from animal reproductive toxicity studies with other endothelin-receptor agonists indicate that use is contraindicated in pregnant women.^[1]

Mechanism of action

Aprocitentan is an endothelin receptor antagonist that inhibits the protein endothelin-1 from binding to endothelin A and endothelin B receptors.^[1][6] Endothelin-1 mediates various adverse effects via its receptors, such as inflammation, cell proliferation, fibrosis, and vasoconstriction.^[1]

Society and culture

Economics

Aprocitentan is developed by Idorsia, which sold it to Janssen and purchased the rights back in 2023, for US$343 million.^[9]

Legal status

Aprocitentan was approved for medical use in the United States in March 2024.^[1]

In April 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Jeraygo, intended for the treatment of resistant hypertension in adults.^[2][10] The applicant for this medicinal product is Idorsia Pharmaceuticals Deutschland GmbH.^[2] Aprocitentan was approved for medical use in the European Union in June 2024.^[2][3]