Table 1.
A wide variety of γ-secretase inhibitors have effects on calcium signaling and Aβ production that are similar in rank-order potency
| Compound | Chemical class | IC50Ca, μM | IC50Aβtot, μM | Notes | Refs. |
|---|---|---|---|---|---|
| IL | Peptide aldehyde | 10 | 8 | Reversible | 17 |
| ILX | Peptide epoxide | 10 | 10 | Irreversible analogue of IL | 17 |
| YIL | Peptide aldehyde | 1 | 0.5 | ELISA data are for Aβ1–40 only | |
| CIL | Peptide aldehyde | 1 | 0.1 | Potent analogue of IL | 17 |
| PIA | Peptide aldehyde | >100 | >100 | Structurally related to IL but inactive | |
| MW-III-36C | (Hydroxyethyl) urea | 2 | 0.5 | Similar to L-685,458 | 22, † |
| MW-III-26A | (Hydroxyethyl) urea | 40 | 25* | Structurally related to MW-III-36C | † |
| CM-265 | Peptide difluoroketone | 30 | 8–25* | Potency varies among different cell types | |
| JT-326 | Peptide | >100 | >100* | Structurally related to CM-265 but inactive |
*
Determined in Chinese hamster ovary cells overexpressing wild-type APP incubated with compound for 6 h; all other data are from N2aWt11 cells incubated with compound for 3–4 h.
†
Wolfe, M. S., Esler, W. P., Kimberly, W. T., Diehl, T. S., Rahmati, T. & Selkoe, D. J. (2000) Soc. Neurosci. 26, 298.9 (abstr.).