JNJ-9350
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: SMOX enzymatic assay using HyPerBlu: IC50 = 10 nM; Horseradish Peroxidase (HRP) Fluorescence Assay: Ki = 9.9 nM (competitive) |
| Selectivity within target family: > 30-fold | PAOX IC50 = 790 nM (PAOX biochemical assay using HyPerBlu) (79-fold); KDM1A (LSD1): IC50 > 60 µM (HyPerBlu assay) |
| Selectivity outside target family | CEREP receptor panel at 10 µM: Off-targets with IC50 < 10 µM: ADORA1 (98.93 % inh.), ADORA2A (74.96 % inh.), ADORA3 (75.06 % inh.) Closest off-targets in the PDSP scan (44 targets) at 10 µM are HTR1D (Ki = 219.42 nM), HTR1B (Ki =477.93 nM), GABA/PBR (Ki = 497.62 nM), HTR2B (Ki = 897.02 nM),OPRK1 (Ki = 1168.96 nM), TMEM97 (Ki = 1924.86 nM) and ADRA2B (Ki = 3579.32 nM). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | CETSA: 91 - 108 % recovery of SMOX (54 °C; IC50 = 1.2. µM) |
| Control compound (100 times less potent than the probe) | JNJ-4545: SMOX enzymatic assay: IC50 > 31 µM; PAOX IC50 = 2.1 µM (PAOX biochemical assay) Closest off-targets in the PDSP scan (44 targets) at 10 µM are OPRK1 (Ki = 197.79 nM), GABA/PBR (Ki = 306.41 nM), CHRM4 (Ki =1307.68 nM), DRD4 (Ki = 3385.32 nM) and DRD3 (Ki = 3603.3 nM). |