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	411.49 g/mol 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.

References

^ "Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure". N Engl J Med. 371: 993–1004. August 30, 2014. doi:10.1056/NEJMoa1409077. PMID 25176015. {{cite journal}}: Unknown parameter |authors= ignored (help)
^ 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.; Maahs, S.; Ksander, G.; Rigel, D. F.; Jeng, A. Y.; Lin, T. H.; Zheng, W.; Dole, W. P. (2009). "Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual-Acting Angiotensin Receptor-Neprilysin Inhibitor (ARNi)". The Journal of Clinical Pharmacology. 50 (4): 401–414. doi:10.1177/0091270009343932. PMID 19934029.
^ Schubert-Zsilavecz, M; Wurglics, M. "Neue Arzneimittel 2010/2011" (Document) (in German)Template:Inconsistent citations {{cite document}}: Cite document requires |publisher= (help)CS1 maint: postscript (link)
^ "Entrez Gene: Membrane metallo-endopeptidase".

Template:Peptidergics

This drug article relating to the cardiovascular system is a stub. You can help Wikipedia by expanding it.

[McMurray-1] "Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure". N Engl J Med. 371: 993–1004. August 30, 2014. doi:10.1056/NEJMoa1409077. PMID 25176015. {{cite journal}}: Unknown parameter |authors= ignored (help)

[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.; Maahs, S.; Ksander, G.; Rigel, D. F.; Jeng, A. Y.; Lin, T. H.; Zheng, W.; Dole, W. P. (2009). "Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual-Acting Angiotensin Receptor-Neprilysin Inhibitor (ARNi)". The Journal of Clinical Pharmacology. 50 (4): 401–414. doi:10.1177/0091270009343932. PMID 19934029.

[Schubert-4] Schubert-Zsilavecz, M; Wurglics, M. "Neue Arzneimittel 2010/2011" (Document) (in German)Template:Inconsistent citations {{cite document}}: Cite document requires |publisher= (help)CS1 maint: postscript (link)

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

[1]

[2]

[3]

[4]

[5]

Mechanism of action

See also

References