TCH-165

TCH-165 is a small molecule modulator of proteasome assembly, which increases 20S levels and facilitates 20S-mediated protein degradation^[1]. IC50 & Target:Proteasome assembly^[1] In Vitro:TCH-165 (0.01-10 μM; 72 hours; RPMI8226 and U87MG cells) treatment inhibits cell growth of RPMI8226 and U87MG cells with IC₅₀ of 1.6 μM and 2.4 μM, respectively^[1].
TCH-165 (0-10 μM; 24 hours; HEK293T cells) treatment enhances ODC degradation is blocked by BTZ indicated that this event is proteasome-mediated. TCH-165 enhances proteolytic degradation in a concentration-dependent manner^[1].
TCH-165 enhances the chymotrypsin-like (CT-L), trypsin-like (Tryp-L) and caspase-like (Casp-L) activities with EC₅₀s of 4.2 μM, 3.2 μM and 4.7 μM, respectively^[1].
TCH-165 enhances 20S-mediated degradation of IDPs, α-syn, and tau in vitro, and does not induce the degradation of structured proteins such as GAPDH^[1].
TCH-165-treated cells display a decrease in the assembled 26S and an increase in the 20S proteasome. TCH-165 regulates the dynamic equilibrium between the 20S and 26S proteasome complexes, favoring 20S-mediated protein degradation^[1].