PPTN
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd>/sub>) | Surpasses criterion: For P2RY14: IC50 = 0.5 nM (FLIPR assay); Ki = 2.3 nM (Binding assay); Ki = 35 nM (Binding assay w/ 2% HSA) |
| Selectivity within target family: > 30-fold | Surpasses criterion: >10,000-fold selectivity over other P2RY* receptorsShows off-target activity in the PDSP scan: the closest hits are DRD3 (Ki = 884.3 nM), TMEM97 (Ki = 1120.99 nM) , SIGMAR1 (Ki = 1180.59 nM), ADRA2B (Ki = 2561.53 nM) |
| Selectivity outside target family | Closest off-targets (Panlabs): CYSLTR1 (h): IC50 = 560 nM @ 1µM, HRH2 (h): IC50 = 1390 nM @ 10 µM, SLC6A3 (Dopamine Transporter) (h): IC50 = 2310 nM @ 10 µMKINOMEScan with 468 targets at 1 µM: clean |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses |
| Control compound (100 times less potent than the probe) | Surpasses criterion: P2RY14 potency > 4000x less; IC50 = 4381 nM (FLIPR assay); Ki = 8614 nM (Binding assay); Ki > 100 µM (Binding assay w/ 2% HSA); Shows off-target activity in the PDSP scan: the closest hits are SIGMAR1 (Ki = 1168.69 nM), TMEM97 (Ki = 1704.51 nM) , ADRA2B (Ki = 1836.54 nM)KINOMEScan with 468 targets at 1 µM: clean |