Sacubitril

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Sacubitril
Sacubitril skeletal.svg
Clinical data
Other namesAHU-377
License data
ATC code
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H29NO5
Molar mass411.49 g/mol g·mol−1
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[edit]

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

See also[edit]

References[edit]

  1. ^ 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 (11): 993–1004. doi:10.1056/NEJMoa1409077. PMID 25176015.CS1 maint: uses authors parameter (link)
  2. ^ Solomon, SD. "HFpEF in the Future: New Diagnostic Techniques and Treatments in the Pipeline". Boston. p. 48. Retrieved 2012-01-26.
  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.
  4. ^ Schubert-Zsilavecz, M; Wurglics, M. "Neue Arzneimittel 2010/2011" (in German) Cite journal requires |journal= (help)
  5. ^ "Entrez Gene: Membrane metallo-endopeptidase".