Reactome | CES1 hydrolyses sacubitril to sacubitrilat

CES1 hydrolyses sacubitril to sacubitrilat

Stable Identifier

R-HSA-9727567

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, lipid droplet

ReviewStatus

5/5

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CES1 hydrolyses sacubitril to sacubitrilat

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Sacubitril (AHU377), a neprilysin inhibitor, is a component of LCZ696 a combination drug also containing the angiotensin receptor blocker valsartan. LCZ696 is indicated for heart failure and hypertension. To exert its activity, sacubitril requires activation to its active form, sacubitrilat (LBQ657). Liver carboxylesterase 1 (CES1) trimer has been demonstrated to hydrolyse (de-ethylate) sacubitril to sacubitrilat (Shi et al. 2016).

Literature References

PubMed ID	Title	Journal	Year
26817948	Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation Shi, J, Wang, X, Nguyen, J, Wu, AH, Bleske, BE, Zhu, HJ	Drug Metab Dispos	2016