BI-1230
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Inhibition effects were evaluated in an enzymatic assay using a NS3-NS4A heterodimer and a fluorogenic substrate: IC50 = 6.7 nM |
| Selectivity within target family: > 30-fold | Surpasses criterion:Selectivity tested for 6 human serine proteases @ 10 µM (Eurofins-Cerep): Only hit is CTSG at 63% inhibition (est. IC50 = 6 µM). Clean Eurofins-Cerep panel for non-serine proteases tested @ 10 µM. |
| Selectivity outside target family | Human F2R (PAR1) cell based antagonist effect assay @ 10 µM: 59.6 % inhibition (Eurofins-Cerep). Shows weak off-target activity in the PDSP scan: the closest hit is ADRA2C (Ki = 3290.99 nM)KINOMEScan with 468 targets at 1 µM: Closest off-targets of primary data (% Ctrl) are STK38L (43), MELK (44). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | HCVPV RNA replication Luciferase reporter assay with human hepatoma Huh-7 cells (3-day incubation): Genotype 1a (EC50 = 4.6 nM); genotype 1b (EC50 < 1.8 nM ) |
| Control compound (100 times less potent than the probe) | BI-1675 (IC50 > 4870 nM); Clean PDSP scanKINOMEScan with 468 targets at 1 µM: Closest off-targets of primary data (% Ctrl) are MYO3B (38), MATK (41), DYRK1B (46) |