GSM1
| Target | Gamma secretase catalytic subunit (PSEN1) |
| Mode of action | Modulator |
| Control | GSM-NC |
| Orthogonal probe | MRK-560 |
| Recommended cellular usage concentration | ≤ 1 µM |
| In vivo use | yes |
| Donated by | MSD |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | No direct measure of ‘biochemical potency’ possible for an allosteric modulator of protein complex. |
| Selectivity within target family: > 30-fold | GS is a large complex, there are no near family aspartyl proteases; the compound was profiled in a large panel of off-targets. |
| Selectivity outside target family | GSM1 was found to be a 5-HT re-uptake inhibitor (IC50 = 30 nM). MSD Pharma/Taiwan screen of 165 enzymes and receptors: Closest hits are (IC50): SLC6A4 (13 nM), SLC6A3 (536 nM), Na channel site 2 (1 µM); Shows activity on the PDSP scan: the closest hits are SLC6A4 (SERT) (Ki = 24 nM) and SLC6A3 (Ki = 191 nM). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Cellular potency on APP (Aβ42) is < 100 nM |
| Control compound (100 times less potent than the probe) | The control is > 10 µM in cells. Shows activity on the PDSP scan: the closest hits are SLC6A4 (SERT) (Ki = 390.58 nM) and TMEM97 (Ki = 834.75 nM). |