Sacubitril

Sacubitril
Clinical data
Other names	AHU-377
License data	EU EMA: by INN;
ATC code	C09DX04 (WHO) (combination with valsartan);
Identifiers
	IUPAC name 4-{[(2S,4R)-1-(4-Biphenylyl)-5-ethoxy-4-methyl-5-oxo-2-pentanyl]amino}-4-oxobutanoic acid;
CAS Number	149709-62-6 ;
PubChem CID	9811834;
DrugBank	DB09292;
ChemSpider	7987587;
UNII	17ERJ0MKGI;
KEGG	D10225;
CompTox Dashboard (EPA)	DTXSID20164370 ;
Chemical and physical data
Formula	C24H29NO5
Molar mass	411.498 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCOC(=O)[C@H](C)C[C@@H](CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)CCC(=O)O;
	InChI InChI=1S/C24H29NO5/c1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19/h4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28)/t17-,21+/m1/s1; Key:PYNXFZCZUAOOQC-UTKZUKDTSA-N;

Sacubitril (/səˈkjuːbɪtrɪl/; INN) is an antihypertensive drug used in combination with valsartan. The combination drug sacubitril/valsartan, known during trials as LCZ696 and marketed under the brand name Entresto, is a treatment for heart failure.[1] It was approved under the FDA's priority review process for use in heart failure on July 7, 2015.

Mechanism of action

Sacubitril is a prodrug that is activated to sacubitrilat (LBQ657) by de-ethylation via esterases.[2] Sacubitrilat inhibits the enzyme neprilysin,[3] which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure–lowering peptides that work mainly by reducing blood volume.[4] In addition, neprilysin degrades a variety of peptides including bradykinin,[5] an inflammatory mediator, exerting potent vasodilatory action.

Sacubitril activation to sacubitrilat

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References

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. (September 2014). "Angiotensin-neprilysin inhibition versus enalapril in heart failure". The New England Journal of Medicine. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. PMID 25176015.
Solomon SD. "HFpEF in the Future: New Diagnostic Techniques and Treatments in the Pipeline". Boston. p. 48. Retrieved 2012-01-26.
Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, et al. (April 2010). "Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi)". Journal of Clinical Pharmacology. 50 (4): 401–14. doi:10.1177/0091270009343932. PMID 19934029.
Schubert-Zsilavecz M, Wurglics M. "Neue Arzneimittel 2010/2011" (in German). Cite journal requires |journal= (help)
"Entrez Gene: Membrane metallo-endopeptidase".

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[McMurray-1] McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. (September 2014). "Angiotensin-neprilysin inhibition versus enalapril in heart failure". The New England Journal of Medicine. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. PMID 25176015.

[Solomon-2] Solomon SD. "HFpEF in the Future: New Diagnostic Techniques and Treatments in the Pipeline". Boston. p. 48. Retrieved 2012-01-26.

[Gu-3] Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, et al. (April 2010). "Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi)". Journal of Clinical Pharmacology. 50 (4): 401–14. doi:10.1177/0091270009343932. PMID 19934029.

[Schubert-4] Schubert-Zsilavecz M, Wurglics M. "Neue Arzneimittel 2010/2011" (in German). Cite journal requires |journal= (help)

[entrez-5] "Entrez Gene: Membrane metallo-endopeptidase".

Sacubitril

Mechanism of action

See also

References