MRK-560
| Target | Gamma secretase catalytic subunit (PSEN1) |
| Targeted domain | Protease domain |
| Mode of action | Inhibitor |
| Control | GSI-NC |
| Orthogonal probe | GSM1 |
| Recommended cellular usage concentration | ≤ 100 nM |
| In vivo use | Yes |
| Donated by | MSD |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Binding/displacement data << 100 nM |
| Selectivity within target family: > 30-fold | Gamma secretase 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 | All off-targets out of 171 enzymes and receptors are > 100-fold less potent. MRK-560 demonstrated activity in the SLC18A2 (Monoamine Transporter) assay with an IC50 of 213 nM. 6 other off-targets were found between 2 and 10 µM. Clean PDSP scan. |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: picomolar cellular potency |
| Control compound (100 times less potent than the probe) | Surpasses criterion: The control is > 1000-fold less potent in cells; Note: Shows off-target activity in the PDSP scan: the closest hits are HTR2B (Ki = 21 nM) and SIGMAR1 (Ki =223 nM). |