In vitro activity: TCID is selective for UCH-L3 over UCH-L1 by over 100-fold. NU6027 (10 μM) does not promote YFP-GLT-1 accumulation in intracellular vesicles in transfected MDCK cells, while LDN-57444 (10 μM) promotes YFP-GLT-1 accumulation. NU6027 (10 μM) does not produce long-term lysosomal degradation of GLT-1, while LDN-57444 (10 μM) has such effect. TCID (10 μM) diminishes GlyT2 ubiquitination in brainstem and spinal cord primary neurons, which is more pronounced when UCHL1 is inhibited and when cells are exposed to these inhibitors for longer periods.
Cell Assay: In transfected MDCK cells, TCID (10 μm for 30 mins) was not able to affect the UCH-L1 inhibitor promoted accumulation of YFP-GLT-1 in intracellular vesicles. |