PTC-553

PTC-553 (24 h) is a MAPT splicing modulator hit in the HEK293T-MAPT minigene assay, where the four hit compounds have an EC_2X of 5-21 nM for 3R MAPT^[1].
PTC-553 (24 h) in 8-week differentiated WT iPSC-derived cortical neurons dose-dependently reduces 4R tau and increases 3R tau^[1].
PTC-553 (96 h and 3 weeks) in tau-P301L iPSC-derived neurons reduces 4R MAPT mRNA after 96 h but has weak 4R tau-lowering activity (50% maximal reduction at 96 h; EC₅₀ 89.4-355.0 nM) and no clear 3-week 4R MAPT mRNA dose response^[1].
PTC-553 (96 h and 3 weeks) in tau-S305N iPSC-derived neurons promotes dose-dependent 3R MAPT increase and 4R MAPT decrease after 96 h but shows only modest 4R MAPT mRNA activity after 3 weeks^[1].
PTC-553 (0-1e3 nM; 24 h) was tested in 8-week-old control tau-WT human iPSC-derived neurons, and 4R/3R tau protein levels were assessed by western blot without an explicit potency value in the supplied image.