Sacubitril
![]() | |
Clinical data | |
---|---|
Synonyms | AHU-377 |
License data | |
ATC code | |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
Chemical and physical data | |
Formula | C24H29NO5 |
Molar mass | 411.49 g/mol |
3D model (JSmol) | |
| |
|
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.
![](../I/m/Sacubitril_activation.svg.png)
See also
References
- ↑ John J.V. McMurray, Milton Packer, Akshay S. Desai, et al. for the PARADIGM-HF Investigators and Committees (August 30, 2014). "Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure". N Engl J Med. 371: 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.; 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" (in German)
- ↑ "Entrez Gene: Membrane metallo-endopeptidase".