2-PPA

2-PPA is a lysosomal potassium and proton channel TMEM175 pore blocker.2-PPA binds at a TMEM175 pore site to occlude potassium and proton ion permeation pathways. 2-PPA increases lysosomal macromolecule catabolism, accelerates macropinocytosis. 2-PPA binds to hepatic protein in covalent. 2-PPA can be used for the research of Parkinson's disease^[1][2]. In Vitro:2-PPA (1-1000 μM) potently inhibits human TMEM175-mediated K⁺ flux, with an IC₅₀ of 31 μM^[1].
2-PPA binds as a pore blocker to the cytosolic region of the open-state human TMEM175 pore, occluding the ion permeation pathway via specific interactions with channel residues Ser45 and Ala42^[1].
2-PPA (3-1000 μM) potently and selectively inhibits human TMEM175-mediated Kv3.1 currents in HEK293T cells, with an IC₅₀ of 32 μM^[1].
2-PPA (3-1000 μM) inhibits human TMEM175-mediated proton flux in HEK293T cells with an IC₅₀ of 30 μM at pH 4.5^[1].
2-PPA (300 μM; 1 h) accelerates lysosomal catabolism and macropinocytosis in wild-type MEFs, MIA PaCa-2, SH-SY5Y, PANC-1, and HeLa cells via specific inhibition of TMEM175^[1].
2-PPA (300 μM; 1 h) stimulates lysosomal cathepsin B activity in wild-type MEFs via indirect modulation of lysosomal function, without directly altering cathepsin enzymatic activity^[1]. In Vivo:2-PPA (130 mg/kg; i.p.; single dose) administration to rats results in covalent binding to hepatic protein that is increased by 25% with Clofibric acid (HY-B1415) pretreatment, and decreased by 25% and 29% with Fenofibrate (HY-17356) and Gemfibrozil (HY-B0258) pretreatment, respectively, due to differential modulation of hepatic reactive metabolite levels^[2].