Zilebesiran

Last updated

Zilebesiran
Zilebesiran.svg
Clinical data
Other namesAD-85481, ALN-85481, ALN-AGT01
Legal status
Legal status
  • Investigational
Identifiers
  • sodium;[(2S,4R)-1-[12-[[1-[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]-2-[[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]methyl]-3-[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-methyloxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]propan-2-yl]amino]-12-oxododecanoyl]-4-hydroxypyrrolidin-2-yl]methyl [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-yl] phosphate
CAS Number
PubChem CID
UNII
Chemical and physical data
Formula C89H152N16NaO36P
Molar mass 2076.235 g·mol−1
3D model (JSmol)
  • C[C@@H]1[C@@H]([C@@H]([C@H]([C@@H](O1)OCCCCC(=O)NCCCNC(=O)CCOCC(COCCC(=O)NCCCNC(=O)CCCCO[C@H]2[C@@H]([C@H]([C@H]([C@H](O2)CO)O)O)NC(=O)C)(COCCC(=O)NCCCNC(=O)CCCCO[C@H]3[C@@H]([C@H]([C@H]([C@H](O3)CO)O)O)NC(=O)C)NC(=O)CCCCCCCCCCC(=O)N4C[C@@H](C[C@H]4COP(=O)([O-])O[C@@H]5[C@H](O[C@H]([C@@H]5OC)N6C=NC7=C(N=CN=C76)N)CO)O)NC(=O)C)O)O.[Na+]
  • InChI=InChI=1S/C89H153N16O36P.Na/c1-54-75(121)78(124)71(100-55(2)109)86(137-54)133-37-17-14-23-63(113)91-31-20-34-94-66(116)28-40-130-49-89(50-131-41-29-67(117)95-35-21-32-92-64(114)24-15-18-38-134-87-72(101-56(3)110)79(125)76(122)60(45-106)139-87,51-132-42-30-68(118)96-36-22-33-93-65(115)25-16-19-39-135-88-73(102-57(4)111)80(126)77(123)61(46-107)140-88)103-69(119)26-12-10-8-6-7-9-11-13-27-70(120)104-44-59(112)43-58(104)48-136-142(127,128)141-81-62(47-108)138-85(82(81)129-5)105-53-99-74-83(90)97-52-98-84(74)105;/h52-54,58-62,71-73,75-82,85-88,106-108,112,121-126H,6-51H2,1-5H3,(H,91,113)(H,92,114)(H,93,115)(H,94,116)(H,95,117)(H,96,118)(H,100,109)(H,101,110)(H,102,111)(H,103,119)(H,127,128)(H2,90,97,98);/q;+1/p-1/t54-,58+,59-,60-,61-,62-,71-,72-,73-,75+,76+,77+,78-,79-,80-,81-,82-,85-,86-,87-,88-;/m1./s1
  • Key:FUHMXNACFUZXIQ-ZHSRMXMESA-M

Zilebesiran is an investigational new drug developed by Roche and Alnylam that is being evaluated for the treatment of high blood pressure.

It is small interfering RNA that is administered subcutaneously twice annually to lower blood pressure in people already taking other antihypertensive drugs. [1] [2] [3] It works by impeding the synthesis of angiotensinogen in the liver. [4] [5]

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Hypertension</span> Long-term high blood pressure in the arteries

Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide.

<span class="mw-page-title-main">Beta blocker</span> Medications for abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most people.

A hypertensive urgency is a clinical situation in which blood pressure is very high with minimal or no symptoms, and no signs or symptoms indicating acute organ damage. This contrasts with a hypertensive emergency where severely high blood pressure is accompanied by evidence of progressive organ or system damage.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

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 a reduction of blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%. It 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, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Atenolol</span> Beta blocker medication

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Indapamide</span> Thiazide-like diuretic drug

Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Reserpine</span> Drug used to treat high blood pressure

Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available in 2012.

<span class="mw-page-title-main">Doxazosin</span> Group of stereoisomers

Doxazosin, sold under the brand name Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia, hypertension, and post-traumatic stress disorder (PTSD). For high blood pressure, it is a less preferred option. It is taken by mouth.

<span class="mw-page-title-main">Hydralazine</span> Anti-hypertension medication

Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours.

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

Olmesartan, sold under the brand name Benicar among others, is a medication used to treat high blood pressure (hypertension). It is taken orally. Versions are available as the combination olmesartan/hydrochlorothiazide and olmesartan/amlodipine. It is available as a prodrug, olmesartan medoxomil.

<span class="mw-page-title-main">Carvedilol</span> Blood pressure medication

Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction. Beta-blockers as a collective medication class are not recommended as routine first-line treatment of high blood pressure for all patients, due to evidence demonstrating less effective cardiovascular protection and a less favourable safety profile when compared to other classes of blood pressure-lowering medications.

<span class="mw-page-title-main">Perindopril</span> High blood pressure medication

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease. As a long-acting ACE inhibitor, it works by relaxing blood vessels and decreasing blood volume. As a prodrug, perindopril is hydrolyzed in the liver to its active metabolite, perindoprilat. It was patented in 1980 and approved for medical use in 1988.

Hypertensive encephalopathy (HE) is general brain dysfunction due to significantly high blood pressure. Symptoms may include headache, vomiting, trouble with balance, and confusion. Onset is generally sudden. Complications can include seizures, posterior reversible encephalopathy syndrome, and bleeding in the back of the eye.

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

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

<span class="mw-page-title-main">Alacepril</span> Antihypertensive drug of the ACE inhibitor class

Alacepril (INN) is an ACE inhibitor medication indicated as a treatment for hypertension. The medication metabolizes to captopril and desacetylalacepril. Alacepril is primarily used to treat hypertension, and in some cases, renovascular hypertension. It's often combined with other medications, particularly other blood pressure lowering classes of medications like thiazide diuretics to maximize its effectiveness.

<span class="mw-page-title-main">Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial</span>

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, also known as ALLHAT, was a randomized, double-blind, active-controlled study comparing at the same time, four different classes of antihypertensive drugs with the rate of coronary heart disease (CHD) events in ‘high-risk’ people with hypertension. Participants were initially randomised to chlorthalidone (diuretic) versus doxazosin, lisinopril (ACE-inhibitor), and amlodipine.

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

Aprocitentan, sold under the brand name Tryvio, is a medication used to treat hypertension. It is developed by Idorsia. It is taken by mouth.

References

  1. Carvalho, Thiago (2023). "RNA interference treatment targeting angiotensinogen lowers blood pressure". Nature Medicine. 29 (12): 2962–2963. doi:10.1038/d41591-023-00091-x. ISSN   1078-8956. PMID   37845541.
  2. Khan, Rida S.; Frishman, William H. (22 February 2024). "Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis". Cardiology in Review. doi:10.1097/CRD.0000000000000645. PMID   38385680.
  3. Waldron, James (5 March 2024). "2nd win for Alnylam RNAi blood pressure med strengthens Roche's $2.8B biobucks bet". Fierce Biotech. Retrieved 6 March 2024.
  4. Desai, Akshay S.; Webb, David J.; Taubel, Jorg; Casey, Sarah; Cheng, Yansong; Robbie, Gabriel J.; et al. (20 July 2023). "Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension" (PDF). New England Journal of Medicine. 389 (3): 228–238. doi:10.1056/NEJMoa2208391. hdl: 20.500.11820/9ec1c393-058a-4fe7-8e8f-df207dcdfb85 . PMID   37467498.
  5. Bakris, George L.; et al. (5 March 2024). "RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial". JAMA. 331 (9): 740–749. doi:10.1001/jama.2024.0728. PMC   10873804 . PMID   38363577.