Sacubitril

Sacubitril

Clinical data
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
Synonyms	AHU-377; AHU377
CAS Number	149709-62-6
PubChem (CID)	9811834
DrugBank	DB09292
ChemSpider	7987587
KEGG	D10225
Chemical and physical data
Formula	C24H29NO5
Molar mass	411.49 g/mol
3D model (Jmol)	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 (/səˈkjuːbᵻtrɪl/;^[1] INN developmental code name AHU-377) is an antihypertensive drug used in combination with valsartan. The combination drug valsartan/sacubitril, known during trials as LCZ696 and marketed under the brand name Entresto, is a treatment for heart failure.^[2] It was approved under the FDA's priority review process for use in heart failure on July 7, 2015.

Mechanism of action

Sacubitril activation to sacubitrilat

Sacubitril is a prodrug that is activated to sacubitrilat (LBQ657) by de-ethylation via esterases.^[3] Sacubitrilat inhibits the enzyme neprilysin,^[4] which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure-lowering peptides that work mainly by reducing blood volume.^[5]

See also

• Omapatrilat

References

1. "sacubitril - Dictiome pronunciation database". Dictiome. Retrieved 19 April 2016.
2. 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.
3. Solomon, SD. "HFpEF in the Future: New Diagnostic Techniques and Treatments in the Pipeline". Boston. p. 48. Retrieved 2012-01-26.
4. 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.
5. Schubert-Zsilavecz, M; Wurglics, M. "Neue Arzneimittel 2010/2011." (in German)