JNJ-65355394
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Fluorescence-based enzymatic assay: IC50 = 1.3 nM Time dependent inhibition: t = 0 (Ki = 1.1 nM); t = 15 min (Ki = 0.035 nM)Kinetic profile: kinact = 0.0036 1/min; kinact/Ki = 3.27 1/(µM*s) |
| Selectivity within target family: > 30-fold | HEXA IC50 > 10 µM |
| Selectivity outside target family | CEREP panel (54 targets) at 10 µM: Closest hits are [% inhibition]: rat OPRK1 (78), rat ADORA2A (69); human OPRM1 PDSP scan clean with one off-target: OPRK1 Ki = 773.3 nM |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Cell-based OGA assay: human IC50 = 3.9 nM; mouse IC50 = 8.1 nM |
| Control compound (100 times less potent than the probe) | JNJ-73924149: Fluorescence-based enzymatic assay (IC50 > 10 µM); cell-based hOGA assay (IC50 > 1000 nM)Closest off-targets in the PDSP scan are SIGMAR1 (Ki = 63.33 nM) and TMEM97 (Ki =1399.16 nM). |