Zofenoprilat

Zofenoprilat is an inhibitor of angiotensin-converting enzyme (ACE; IC₅₀ = 8 nM for the rabbit lung enzyme) and an active metabolite of the prodrug zofenopril (Item No. 29525).^1,2 It inhibits angiotensin I- or bradykinin-induced contractions of isolated guinea pig ileum (EC₅₀s = 3 and 1 nM, respectively).¹ Zofenoprilat (10 nM) decreases basal endothelin-1 secretion and nitric oxide (NO) production, as well as prevents TNF-α-induced increases in reactive oxygen species (ROS) and decreases in glutathione (GSH) levels, in human umbilical vein endothelial cells (HUVECs).³ It protects primary human cardiac microvascular endothelial cells against doxorubicin-induced cytotoxicity when used at a concentration of 10 µM.⁴ Zofenoprilat (10 µM) also increases hydrogen sulfide (H₂S) production in, and adhesion, migration, and proliferation of, HUVECs.⁵ It reduces end diastolic pressure and lactate dehydrogenase (LDH) release in a Langendorff isolated perfused rat heart model of ischemia-reperfusion injury when used at a concentration of 400 µM.²

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1. DeForrest, J.M., Waldron, T.L., Krapcho, J., et al. Preclinical pharmacology of zofenopril, an inhibitor of angiotensin I converting enzyme. J. Cardiovasc. Pharmacol. 13(6), 887-894 (1989).

2. Grover, G.J., Sleph, P.G., Dzwonczyk, S., et al. Effects of different angiotensin-converting enzyme (ACE) inhibitors on ischemic isolated rat hearts: Relationship between cardiac ACE inhibition and cardioprotection. J. Pharmacol. Exp. Ther. 257(3), 919-929 (1991).

3. Desideri, G., Grassi, D., Croce, G., et al. Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: Evidence of an oxidant-sensitive pathway. Mediators Inflamm. 305087 (2008).

4. Monti, M., Terzuoli, E., Ziche, M., et al. The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis. Pharmacol. Res. 76, 171-181 (2013).

5. Terzuoli, E., Monti, M., Vellecco, V., et al. Characterization of zofenoprilat as an inducer of functional angiogenesis through increased H₂S availability. Br. J. Pharmacol. 172(12), 2961-2973 (2015).