Aprocitentan

Last updated

Aprocitentan
Aprocitentan.svg
Clinical data
Trade names Tryvio
Other namesACT-132577
AHFS/Drugs.com Tryvio
Routes of
administration
By mouth
Drug class Antihypertensive
ATC code
Legal status
Legal status
Identifiers
  • 5-(4-Bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C16H14Br2N6O4S
Molar mass 546.19 g·mol−1
3D model (JSmol)
  • C1=CC(=CC=C1C2=C(N=CN=C2OCCOC3=NC=C(C=N3)Br)NS(=O)(=O)N)Br
  • 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, 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]

Contents

Aprocitentan is a dual endothelin-1 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]

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. [8]

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] [9] 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]

Related Research Articles

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Enalapril</span> ACE inhibitor medication

Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Fluticasone/salmeterol</span> Formulation used in the management of asthma and chronic obstructive pulmonary disease

Fluticasone/salmeterol, sold under the brand name Advair among others, is a fixed-dose combination medication containing fluticasone propionate, an inhaled corticosteroid; and salmeterol, a long-acting beta2‑adrenergic agonist. It is used in the management of asthma and chronic obstructive pulmonary disease (COPD). It is used by inhaling the medication into the lungs.

Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Bosentan</span> Medication

Bosentan, sold under the brand name Tracleer among others, is a dual endothelin receptor antagonist medication used in the treatment of pulmonary artery hypertension (PAH).

Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

<span class="mw-page-title-main">Ambrisentan</span> Chemical compound

Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of pulmonary hypertension. It is an endothelin receptor antagonist.

<span class="mw-page-title-main">Azilsartan</span> Chemical compound

Azilsartan, sold under the brand name Edarbi among others, is used for the treatment of hypertension. It is used as the prodrug azilsartan medoxomil, is an angiotensin II receptor antagonist, and was developed by Takeda.

<span class="mw-page-title-main">Actelion</span> Swiss biopharmaceutical company

Actelion Pharmaceuticals Ltd. is a pharmaceuticals and biotechnology company established in December 1997, headquartered in Allschwil near Basel, Switzerland.

<span class="mw-page-title-main">Macitentan</span> Chemical compound

Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist developed by Actelion and approved for the treatment of pulmonary arterial hypertension (PAH). Macitentan is a dual endothelin receptor antagonist, 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.

<span class="mw-page-title-main">Finerenone</span> Chemical compound

Finerenone, sold under the brand name Kerendia and Firialta, is a medication used to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes. Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA). It is taken orally.

<span class="mw-page-title-main">Erdafitinib</span> Chemical compound

Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.

<span class="mw-page-title-main">Daridorexant</span> Medication used to treat insomnia

Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth.

Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

Teclistamab, sold under the brand name Tecvayli, is a human bispecific monoclonal antibody used for the treatment of relapsed and refractory multiple myeloma. It is a bispecific antibody that targets the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells.

<span class="mw-page-title-main">Sparsentan</span> Medication

Sparsentan, sold under the brand name Filspari, is a medication used for the treatment of primary immunoglobulin A nephropathy. Sparsentan is an endothelin and angiotensin II receptor antagonist. It is taken by mouth.

Niraparib/abiraterone acetate, sold under the brand name Akeega, is a fixed-dose combination anti-cancer medication used for the treatment of prostate cancer. It contains niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor.

Macitentan/tadalafil, sold under the brand name Opsynvi, is a fixed dose combination medication used for the treatment of pulmonary arterial hypertension. It contains macitentan, an endothelin receptor antagonist (ERA); and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor.

References

  1. 1 2 3 4 5 6 7 8 9 10 "Tryvio- aprocitentan tablet, film coated". DailyMed. 29 March 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024.
  2. 1 2 3 4 "Jeraygo EPAR". European Medicines Agency . 25 April 2024. Archived from the original on 13 June 2024. Retrieved 13 June 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 1 2 "Jeraygo PI". Union Register of medicinal products. 28 June 2024. Retrieved 5 July 2024.
  4. 1 2 3 "US FDA approves Idorsia's once-daily Tryvio (aprocitentan) - the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with other antihypertensives" (Press release). Idorsia. 20 March 2024. Archived from the original on 28 April 2024. Retrieved 28 April 2024 via PR Newswire.
  5. Ojha, Utkarsh; Ruddaraju, Sanjay; Sabapathy, Navukkarasu; Ravindran, Varun; Worapongsatitaya, Pitchaya; Haq, Jeesanul; et al. (2022). "Current and Emerging Classes of Pharmacological Agents for the Management of Hypertension". American Journal of Cardiovascular Drugs. 22 (3): 271–285. doi:10.1007/s40256-021-00510-9. PMC   8651502 . PMID   34878631.
  6. 1 2 Xu, Jingjing; Jiang, Xiaohua; Xu, Suowen (November 2023). "Aprocitentan, a dual endothelin-1 (ET-1) antagonist for treating resistant hypertension: Mechanism of action and therapeutic potential". Drug Discovery Today. 28 (11): 103788. doi:10.1016/j.drudis.2023.103788. PMID   37742911.
  7. "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
  8. Deswal, Phalguni (6 September 2023). "Idorsia reacquires aprocitentan rights from Janssen for $343m". Pharmaceutical Technology. Archived from the original on 8 November 2023. Retrieved 8 November 2023.
  9. "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2024". European Medicines Agency (Press release). 26 April 2024. Archived from the original on 5 July 2024. Retrieved 13 June 2024.

Further reading