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JNJ-78911118

2D structure
Target GRIN2A 
Targeted domain GRIN1/GRIN2A interface
Mode of action Negative Allosteric Modulator
Control JNJ-77914993
Orthogonal probe TP-050 
Recommended cellular usage concentration ≤ 10 µM
In vivo use Yes
Donated by Johnson & Johnson


Probe criteria


Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) Surpasses criterion: Fully blocks GRIN1/GRIN2A-induced calcium flux with IC50 = 40 nM (FLIPR)
Displaces the GRIN1/GRIN2A interface binding radioligand [3H]-1 in rat hippocampal neuron membranes in a concentration dependent manner: Ki =78 nM
Selectivity within target family: > 30-fold > 200 fold selectivity over other homomeric GluN2 family members: GRIN2B, GRIN2C, GRIN2D all IC50 > 50 µM (FLIPR)
Selectivity outside target family Cerep panel (Receptors, Transporters, Ion-Channels) 77 targets at 10 µM: clean; Kinase panel (373 targets, Cerep) at 1 µM: clean
On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 Surpasses criterion: Reduced glutamate/glycine-evoked currents in Xenopus oocytes:
  • Fully blocked rat diheteromeric GRIN1/GRIN2A receptors (IC50 = 44nM)
  • Showed nominal block and reduced potency vs. rat triheteromeric receptors in oocytes (two electrode voltage clamp): GRIN1/GRIN2A/GRIN2B (IC50 = 202 nM; 53% maximal block); GRIN1/GRIN2A/GRIN2C (IC50 = 88 nM; 83% maximal block); GRIN1/GRIN2A/GRIN2D (IC50 = 72 nM; 48% maximal block)
Control compound (100 times less potent than the probe) JNJ-77914993: GRIN2A = 48 µM; GRIN2B, GRIN2C, GRIN2D all IC50 > 50 µM (FLIPR)