Donated Chemical Probes

Target	RORC
Targeted domain	Orthosteric site of binding domain
Mode of action	Inverse agonist
Control	JNJ-53721590
Recommended cellular usage concentration	≤ 1 µM
In vivo use	Yes
Synonyms	JNJB44154397
Donated by	Johnson & Johnson

Inhibitor/agonist potency: goal is < 100 nM (IC₅₀, K_d)	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 µM Nuclear 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 % inhibition DiscoverX panel (50 kinases) at 10 µM: all < 50 % inhibition Closest 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))