C004019

C004019 is a small molecule PROTAC capable of targeting tau for selective protein degradation from the cell, while recruiting tau and E3 ligase (Vhl) for selective enhancement of tau ubiquitination and proteollyzation. C004019 is a candidate for AD and related tau protein diseases.

C004019 induced a robust tau clearance via promoting its ubiquitination-proteasome-dependent proteolysis in HEK293 cells with stable or transient overexpression of human tau (hTau), and in SH-SY5Y that constitutively overexpress hTau.[1]

C004019 induced a robust tau clearance in vivo by intracerebral ventricular infusion. Most importantly, both single-dose and multiple-doses (once per 6 days for a total of 5 times) subcutaneous administration of C004019 remarkably decreased tau levels in the brains of wild-type, hTau-transgenic and 3xTg-AD mice with the improvement of synaptic and cognitive functions.[1]

1. Wang W, et al. A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models. Theranostics. 2021;11(11):5279-5295.