TP-050
| Target | GRIN2A |
| Targeted domain | GRIN1/GRIN2A ligand binding domain (Tyr 144) |
| Mode of action | Positive allosteric modulator |
| Control | TP-050n |
| Orthogonal probe | JNJ-78911118 |
| Recommended cellular usage concentration | ≤ 30 µM |
| In vivo use | Yes |
| Synonyms | (R)-9 |
| Donated by | Takeda |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | N/A |
| Selectivity within target family: > 30-fold | Good NMDA-subtype selectivity (Ca2+ influx assay using CHO cells): GRIN2B EC50 > 30 µM, max potentiation < 150 %; > 59-fold selectivity; GRIN2C EC50 > 30 µM, max potentiation < 200 %; GRIN2D EC50 = 9.6 µM, max potentiation < 260 %; 19-fold selectivity; AMPA receptor scintillation proximity (SPA) binding assay: IC50 > 30 µM |
| Selectivity outside target family | SAFETYscan (DiscoverX, 47 targets at 10 µM): 46 target > 10 µM; PDE3A 7.9 μM, 56% inhibition Clean PDSP scan (44 targets) at 10 µM except for GABA/PBR (Ki = 336.06 nM) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: EC50 = 0.51 µM; Max. potentiation at 30 µM: 350 % (Ca2+ influx assay using CHO cells) |
| Control compound (100 times less potent than the probe) | TP-050n: EC50 > 30 µM (> 59 -fold); Max. potentiation at 30 µM: 150 % (Ca2+ influx assay using CHO cells) Clean PDSP scan (44 targets) at 10 µM |