Table 1.
Summary of main chemical scaffolds reported to exert anti-prion effects by directly targeting PrPC.
| Chemical Scaffold | Compound (Figure 1) | KD * | EC50 ** | Effect In Vivo *** | Conclusions |
|---|---|---|---|---|---|
| Acridine derivatives | 1 | ~1mM | ~0.3 µM | Not significant | Primary effects are PrP-independent |
| Phenothiazine derivatives | 2 | >400 µM | ~3 µM | Not significant | Likely acting by inducing PrPC re-localization from the cell surface |
| Tetrapyrroles | 5 | 4.52 µM | 1.6 µM | Prolongation of survival time in prion-infected mice | Low specificity and possible poor pharmacokinetics |
| Diazo dyes | 6 | 1.6 µM | 0.015 µM | Not available | Low specificity |
| Chicago sky blue 6B | 7 | 0.55 µM | Low µM | Not available | Need confirmation |
| Diphenylmethane derivatives | 8 | 5 µM | 1.35 µM | Prolongation of survival time in prion-infected mice | PrPC binding not reproduced in some study |
| Pyridine Dicarbonitriles | 11 | ~20µM | 18.6 µM | Not available | No correlation between anti-prion activity and binding to PrPC |
| Diarylthiazoles | 13 | 3.8 µM | 4 µM | Not available | No correlation between anti-prion activity and binding to PrPC |
| Natural polyphenols | 14 | 0.13 µM | - | Not available | Possible non-specific interaction with PrPC |
| Miscellanea | 17 | 50.8 µM | Not available | Not available | Need confirmation |
| 20 | 19 µM | 3.72 µM | Not available | Need confirmation |
* Reported affinity for PrPC; ** Anti-prion activity measured in cell cultures; *** Tested in prion-infected rodent models and/or human patients.