JNJ-54119936
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Binding to RORC ligand binding domain, TF qKD = 5.3 nM (ThermoFluor Binding Assay) |
| Selectivity within target family: > 30-fold | RORA TF qKD > 75 µM; RORB TF qKD > 75 µMNuclear receptor selectivity: PPARA, PPARD, PPARG, NR1H3, NR1H2, NR1I3, NR1H4, NR3C1, NR1D1, NR1D2, THRA, THRB, VDR, NR1I2, RXRA: No significant ago/antagonism at 3 µM |
| Selectivity outside target family | Cerep Panel (50 targets) at 1 and 10 µM: all < 50 % inhibitionDiscoverX panel (50 kinases) at 10 µM: all < 50 % inhibitionClosest off-targets in the PDSP scan are TMEM97 Ki =636.66 nM, SIGMAR1 Ki =3125.58 nM and ADRA2B Ki = 9223.59 nM. |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion:1-hybrid LBD at 6 µM: IC50 = 30 nM (100 % inhibition)hWB assay at 10 µM: IC50 = 332 nM (82 % inhibition) |
| Control compound (100 times less potent than the probe) | JNJ53721590: TF qKD = 515.7 nM (~ 100 fold) 1-hybrid LBD at 6 µM: IC50 = 670 nM (87% inhibition) (> 20 fold)hWB assay: IC50 > 10 µM (> 30 fold)) |