CES1 hydrolyses sacubitril to sacubitrilat

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).

Sacubitril（AHU377），一种神经肽酶抑制剂，是LCZ696组合药物的组成部分，该药物同时含有血管紧张素受体阻滞剂Valsartan。LCZ696主要用于治疗心力衰竭和高血压。为发挥其活性，Sacubitril需被激活成其活性形式，即Sacubitrilat（LBQ657）。研究表明，肝脏羧酸酯酶1（CES1）三聚体能够将Sacubitril水解（脱乙基）成Sacubitrilat（Shi等，2016年）。