KYP-2047

KYP-2047 is an inhibitor of prolyl endopeptidase (K_i = 0.02 nM for the porcine enzyme).¹ It inhibits hydrogen peroxide-induced aggregation of α-synuclein in SH-SY5Y cells expressing wild-type, α-synuclein^A30P, or α-synuclein^A53T in in vitro models of Parkinson’s disease when used at a concentration of 1 µM.² KYP-2047 (10 µM) decreases lipid peroxidation and the production of reactive oxygen species (ROS) induced by palmitic acid (Item No. 10006627) in HepG2 cells.³ It decreases ileal and pulmonary edema and pulmonary fibrosis in a mouse model of acute lung injury induced by intestinal ischemia-reperfusion when administered at a dose of 2.5 mg/kg.⁴ KYP-2047 (2.5 mg/kg) reduces tumor volume and intratumoral levels of Vegf and Cd34, markers of angiogenesis, in a U87 glioblastoma mouse xenograft model.⁵

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1. Jarho, E.M., Venäläinen, J.I., Huuskonen, J., et al. A cyclopent-2-enecarbonyl group mimics proline at the P₂ position of prolyl oligopeptidase inhibitors. J. Med. Chem. 47(23), 5605-5607 (2004).

2. Myöhänen, T.T., Hannula, M.J., Van Elzen, R., et al. A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson’s disease. Br. J. Pharmacol. 166(3), 1097-1113 (2012).

3. Zhang, J., Jiang, D., Lin, S., et al. Prolyl endopeptidase disruption reduces hepatic inflammation and oxidative stress in methionine-choline-deficient diet-induced steatohepatitis. Life Sci. 270, 119131 (2021).

4. Casili, G., Scuderi, S.A., Lanza, M., et al. The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion. Oncotarget 12(17), 1663-1676 (2021).

5. Scuderi, S.A., Casili, G., Ardizzone, A., et al. KYP-2047, an inhibitor of prolyl-oligopeptidase, reduces glioblastoma proliferation through angiogenesis and apoptosis modulation. Cancers (Basel) 13(14), 3444 (2021).