A-079
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Surpasses criterion: A-967079 potently blocks human TRPA1 with IC50 of 67 nM as determined in a FLIPR-based Ca2+ assay. |
| Selectivity within target family: goal is > 30-fold | Surpasses criterion:A-967079 is >1000-fold selective over other TRP channels (TRPV1, TRPV3, TRPV4, or TRPM8). |
| Selectivity outside target family | Surpasses criterion: A-967079 is >150-fold selective over 75 tested proteins. In a CEREP panel of 75 enzymes, G-protein-coupled receptors, transporters, and ion channels A-967079 exhibited was modest inhibition on ligand binding to SLC6A3 (43%), SLC6A2 (32%), MTNR1A (31%), with no significant effects (<30%) on other 72 proteins. Shows off-target activity in the PDSP scan for SIGMAR1 (Ki = 505.48 nM)KINOMEScan with 468 targets at 1 µM: Closest off-target of primary data (% Ctrl) is ULK2 (46). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: A-967079 blocks AITC (100 µmol/L)-evoked currents in HEK-293F cells transiently overexpressing hTRPA1 (held at -60 mV) with an IC50 of 0.051 µM. |
| Control compound (100 times less potent than the probe) | Surpasses criterion:The control compound A-1115226 has an IC50 of ˃100 µM in vitro. Shows off-target activity in the PDSP scan: the closest hit is SIGMAR1 (Ki = 528.76 nM)KINOMEScan with 468 targets at 1 µM: Closest off-targets of primary data (% Ctrl) are MAP3K13 (23), ZAP70 (38), PIK3CA(Q546K) (46), TAOK3 (46), FLT3(N841I) (49) |