MME:Zn2+ binds sacubitrilat

Stable Identifier
Reaction [binding]
Homo sapiens
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Neprilysin (MME) is responsible for the degradation of atrial and brain natriuretic peptides (NPPA and NPPB respectively), two blood pressure–lowering peptides that work by reducing blood volume (Richards et al. 1990). Sacubitril is an antihypertensive drug used in combination with valsartan for the treatment of hypertension and heart failure (Gu et al. 2010, Kobalava et al. 2016, Kanodia et al. 2020). Sacubitril is a prodrug that is activated to sacubitrilat (LBQ657) by de-ethylation via esterases (Shi et al. 2016). Sacubitrilat inhibits MME, leading to a lowering of hypertension (Zheng et al. 2021). Angiotensin receptor blockade (via valsartan) and neprilysin inhibition (via sacubitril) together may offer superior benefits for the treatment of hypertension and heart failure than ACE inhibitor monotherapy (McMurray et al. 2014).
Literature References
PubMed ID Title Journal Year
19934029 Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi)

Ksander, G, Gu, J, Ligueros-Saylan, M, Sarangapani, R, Maahs, S, Noe, A, Rigel, DF, Lin, TH, Al-Fayoumi, S, Chandra, P, Zheng, W, Dole, WP, Jeng, AY

J Clin Pharmacol 2010
2144260 Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects

Cussans, N, Richards, M, Yandle, T, Sopwith, M, Ikram, H, Frampton, C, Espiner, E

Hypertension 1990
32506827 Safety, Pharmacokinetics, and Pharmacodynamics of TD-0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects

Baldwin, RM, Bourdet, DL, Lo, A, Kanodia, J, Zhou, K, Colley, K

Clin Transl Sci 2020
26990595 Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction

Albrecht, D, Averkov, O, Moiseev, V, Ayalasomayajula, S, Langenickel, TH, Rajman, I, Prescott, MF, Jordaan, P, Kotovskaya, Y, Pal, P, Chandra, P, Kobalava, Z, Pavlikova, E

Cardiovasc Ther 2016
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