TP-040
| Target | OGA |
| Targeted domain | Hydrophobic deep pocket (Tyr219, Trp278) |
| Mode of action | Inhibitor |
| Control | TP-040n |
| Orthogonal probe | JNJ-65355394 |
| Recommended cellular usage concentration | ≤ 10 µM |
| In vivo use | Yes |
| Donated by | Takeda |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Human OGA enzymatic assay: IC50 = 46 nM |
| Selectivity within target family: > 30-fold | HEXB IC50 > 10 µM (> 210-fold) |
| Selectivity outside target family | Kinase panel (277 kinases at 1 µM): clean, all < 50 % inhibitionClosest off-targets in the PDSP scan are (Ki [nM]): HTR2C (373.79), HTR1D (417.5), GABAA/BZP (511.7), HTR2B (699.39), SLC6A2 (1935.54), ADRA2B (2570.64) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Increase in the level of O-GlcNAcylated protein in human neuroblastoma SH-SY5Y cells: EC50 = 450 nM (Glycosylation in-cell western assay) |
| Control compound (100 times less potent than the probe) | TP-040n: Human OGA enzymatic assay: IC50 > 10 µMClosest off-targets in the PDSP scan (PDSP) are (Ki [nM]): HRH3 (99.57), SIGMAR1 (125.1), HRH2 (148.82), HTR2C (266.79), HTR2B (290.75) etc. |