PTC-003

PTC-003 promotes MAPT exon 10 skipping in HEK293T-MAPT minigene cells with an EC_2X of 5.2 nM; it increases endogenous 3R tau protein in U-87 human glioma cells with an EC_1.3X of 7.4 nM^[1].
PTC-003 (0.1-1000 nM; 24 h) decreases 4R tau in WT and tau-P301L iPSC-derived neurons differentiated for 8 weeks, and Western blot detects a corresponding increase in 3R tau in P301L neurons but not in WT neurons^[1].
PTC-003 (1-1000 nM; 96 h-3 weeks) reduces 4R MAPT mRNA in tau-P301L and tau-S305N iPSC-derived neurons^[1].
PTC-003 (0.1-1000 nM (P301L); 1-10000 nM (S305N); 96 h-3 weeks) reduces 4R tau protein in tau-P301L and tau-S305N iPSC-derived neurons, with P301L EC₅₀ = 30.2-83.6 nM and S305N EC₅₀ = 166.6-173.0 nM at 3 weeks; it reduces total tau and multiple pTau species^[1].
PTC-003 treatment reduces insoluble oligomeric pTau S396 in both P301L and S305N FTD iPSC neurons, rescues glutamate-induced neuronal death, and does not alter glutamate receptor protein expression^[1].

PTC-003 (1-10 μM; 96 h) does not reduce neuronal viability and increases viability in tau-S305N iPSC-derived neurons^[1].

PTC-003 (0.1-1 μM; 78 h preincubation; 10 mM glutamate; 18 h) protects tau-P301L and tau-S305N iPSC-derived neurons from glutamate-induced loss of viability^[1].