Zilebesiran

Zilebesiran
Clinical data
Synonyms	AD-85481, ALN-85481, ALN-AGT01
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 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	2380166-33-4;
PubChem CID	155907821;
UNII	E422BH4BRK;
Chemical and physical data
Formula	C89H152N16NaO36P
Molar mass	2,076.23 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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=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 experimental drug made by the pharmaceutical companies Roche and Alnylam.^[1] It is being tested for the treatment of high blood pressure.^[1] It is a small interfering RNA given through the skin twice yearly to lower blood pressure in those taking other antihypertensive drugs.^[1] The drug works by blocking the synthesis of angiotensinogen in human liver.^[1]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3
- 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.
- Khan, Rida S.; Frishman, William H. (February 22, 2024). "Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis". Cardiology in Review. doi:10.1097/CRD.0000000000000645. PMID 38385680.
- Waldron, James (March 5, 2024). "2nd win for Alnylam RNAi blood pressure med strengthens Roche's $2.8B biobucks bet". Fierce Biotech. Retrieved 2024-03-06.
- Bakris, George L.; et al. (March 5, 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.

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[A-1] 1.0 ^1.1 ^1.2 ^1.3
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.

Khan, Rida S.; Frishman, William H. (February 22, 2024). "Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis". Cardiology in Review. doi:10.1097/CRD.0000000000000645. PMID 38385680.

Waldron, James (March 5, 2024). "2nd win for Alnylam RNAi blood pressure med strengthens Roche's $2.8B biobucks bet". Fierce Biotech. Retrieved 2024-03-06.

Bakris, George L.; et al. (March 5, 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.

[2] 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.

[3] Khan, Rida S.; Frishman, William H. (February 22, 2024). "Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis". Cardiology in Review. doi:10.1097/CRD.0000000000000645. PMID 38385680.

[4] Waldron, James (March 5, 2024). "2nd win for Alnylam RNAi blood pressure med strengthens Roche's $2.8B biobucks bet". Fierce Biotech. Retrieved 2024-03-06.

[5] Bakris, George L.; et al. (March 5, 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.

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