TP-004
| Target | METAP2 |
| Mode of action | Inhibitor |
| Control | TPn-004 |
| Recommended cellular usage concentration | 0.2 - 1 µM |
| In vivo use | yes |
| Donated by | Takeda |
Probe criteria
| In vitro potency <100 nM | Surpasses criterion: Biochemical activity: METAP2 IC50 = 7 nM using Mn, 31 nM using Co |
| Selectivity within target family: > 30-fold | METAP2/1 > 1000-fold; Selectivity against other proteases: < 1000 -fold |
| Selectivity outside target family | Selectivity against kinases > 100-fold. TP-004 was evaluated in a Ricerca Comprehensive Pharmacological Profile panel of 100 biological targets (GPCRs, ion channels, transporters and enzymes) + panel of proteases and was found to have a clean selectivity profile at 10 µM (< 50% inhibition). KCNH2 (hERG) is 1 % at 10 µM. Clean PDSP scan with the closest hit on SLC6A3 (Ki = 1679 nM) |
| Significant cell activity | Acumulation of NMet14-3-3ƴ in HUVEC cells: EC50 = 15 nM |
| Control compound (100 times less potent than the probe) | Surpasses criterion:TPn-004: Biochemical activity METAP2 IC50 > 100 µM using Mn |