Table 1.
A description of the properties for peptide- or chemical mediated targeting PROTACs.
| PROTAC | Entityc | Recognize Tau | Linker | Recruit E3 Ligasea | Cell-Penetrating Peptide |
IC50 (μM) | K d value (μM) | In Vivo study | PK study | PMID |
|---|---|---|---|---|---|---|---|---|---|---|
| Peptid-mediated targeting | TH006 | YQQYQDATADEQG | GSGS | ALAPYIP (VHL) | RRRRRRRRa | None | 0.3944 ±0.1589 | Tau degradation in CA3 region of hippocampus | Not reported | 27105281 |
| Peptide 1 | YQQYQDATADEQG | GSGS | LDPETGEYL(Keap1) | RRRRRRRR | None | Not reported | Not reported | Not reported | 29407955 | |
| Chemical-mediated targeting | QC-01–175 | WTb | CRL4CRBN | 8.559 | 1.2 ± 0.44 | Not reported | Not reported | 30907729 | ||
| A152Tb | 1.7 ± 0.54 | |||||||||
| P301Lb | 2.5 ± 1.31 | |||||||||
| T807 | WT | CRL4CRBN | 0.144 | 1.8 ± 0.99 | Not reported | Not reported | 30907729 | |||
| A152T | 2.1 ± 0.50 | |||||||||
| P301L | 1.7 ± 0.77 | |||||||||
| C004019 | Total, pS214 and pS404 tau | VHL | 0.00785 | Not reported | Robust tau clearance in hippocampus and cortex; Improvement of synaptic and cognitive functions | Tmax (h)=0167; Cmax (ng/ml)=10.8; AUClast (h*ng/ml)=8.42 | 33859747 |
a
Represents poly-D-arginine
b
Represents human recombinant biotinylated-tau WT, A152T and P301L, respectively
Tmax: the time point at which the drug concentration was the highest; Cmax: the maximum drug concentration; AUClast: area under the curve (the integral from the beginning to the last point in time).