tnf‐α‐converting enzyme

Apratastat is an orally active, potent, and reversible dual inhibitor of tumor necrosis factor-α converting enzyme (TACE) and matrix metalloproteinases (MMPs) and it also can potently inhibit the release of TNF-α in vitro, ex vivo, and in vivo with IC50s of 144 ng mL in vitro and 81.7 ng mL ex vivo, respectively[1].

MMP-9 inhibitor I is an inhibitor of matrix metalloproteinase-9 (MMP-9) that is selective over MMP-1 and MMP-13 (IC50s = 5, 1,050, and 113 nM, respectively). It also decreases the activity of TNF-α converting enzyme (TACE) in a dose-dependent manner (IC50 = 0.54 μM). MMP-9 inhibitor I decreases TNF-α secretion stimulated by LPS in BV-2 microglial cells when used at concentrations of 50 and 100 μM.

BMS-566394 is a potent, exceptionally selective inhibitor of TNF-α converting enzyme (TACE).

KP-457 is a specific inhibitor of a disintegrin-metalloproteinase 17 (ADAM17) and a TNFα converting enzyme TACE inhibitor that blocks the production of soluble TNF (sTNF).

Zofenoprilat, an angiotensin-converting enzyme (ACE; IC50 = 8 nM for rabbit lung enzyme) inhibitor and the active metabolite of the prodrug zofenopril, effectively counters angiotensin I- or bradykinin-induced contractions in isolated guinea pig ileum (EC50s = 3 and 1 nM, respectively). At a concentration of 10 nM, Zofenoprilat not only diminishes basal endothelin-1 secretion and nitric oxide (NO) production but also safeguards against TNF-α-stimulated increases in reactive oxygen species (ROS) and reductions in glutathione (GSH) levels within human umbilical vein endothelial cells (HUVECs). Furthermore, at 10 µM, it delivers protection to primary human cardiac microvascular endothelial cells from doxorubicin-induced toxicity and enhances hydrogen sulfide (H2S) production, along with the adhesion, migration, and proliferation of HUVECs. Additionally, Zofenoprilat (400 µM) mitigates end diastolic pressure and lactate dehydrogenase (LDH) release, demonstrating therapeutic potential in a Langendorff isolated perfused rat heart model of ischemia-reperfusion injury.