A-1596586
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Surpasses criterion: CFTR: EC50 = 28 nM (CFTR Restoration Trans-Epithelial Current Clamp (TECC) assay) |
| Selectivity within target family: goal is > 30-fold | N/A |
| Selectivity outside target family | Closest off targets at 10 µM are BZD peripheral (95.5 %), ADORA3 (63.9%) and ADRA2B (63.5%).Closest hits in the PDSP scan (43) are GABA/PBR (Ki = 19.59 nM), SIGMAR1 (Ki =314.63 nM) and TMEM97 (Ki =1192.34 nM).KINOMEScan with 468 targets at 1 µM: clean |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: 28 nM EC50 in TECC assay |
| Control compound (100 times less potent than the probe) | Surpasses criterion: Negative control A-1596584 is ~ 8 fold less potent in restoring CFTR surface expression and > 100 fold less potent in restoring CFTR function. Note: The negative control binds the target but doesn’t inhibit the function; it is not functional. The control at 10 µM inhibits TACR1 (92.1 %), Cl- channel (GABA gated) (82.4 %), BZD peripheral (79.1%), CNR2 (73.7 %), ADORA3 (67.7%).Closest hits in the PDSP scan (43) are GABA/PBR (Ki = 217.72 nM), TMEM97 (Ki =583.98 nM) and SIGMAR1 (Ki =2740.31 nM). KINOMEScan with 468 targets at 1 µM: Closest off-target of primary data (% Ctrl) is MYO3B (39) |