BAY-3153
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd>/sub>) | Surpasses criterion: High potency in biochemical CCR1 assay (Ca2+-flux): IC50 = 3 nM (human) / 11 nM (rat) / 81 nM (mice) |
| Selectivity within target family: > 30-fold | Surpasses criterion: Inactive on CCR3 (human); IC50 > 30 µM for human CCR2, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10 and human CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 Shows weak activity in the PDSP scan: The closest off-target is TMEM97 (Sigma2) (Ki = 1476.05 nM)Eurofins-Panlab results from close analog (O-cPr derivative) show one GPCR as off-target @ 10 µM: ADORA3 (60 % inhibition) |
| Selectivity outside target family | Eurofins-Panlab results from close analog (O-cPr derivative) clean with closest off-targets @ 10 µM (% inhibition): MAOB (73 %), MLN (Motilin) (69 %) |
| On target cell activity for secreted targets: appropriate alternative such as mouse model or other mechanistic biological assay | Surpasses criterion: Suitable pharmacokinetic profile for in vivo studies; in vivo efficacy on infiltrating macrophages in experimental renal ischemia/reperfusion model in mice |
| Control compound (100 times less potent than the probe) | Surpasses criterion: BAY-173 with 400-fold less in vitro potency (IC50 = 1200 nM (human), 8500 nM (mice); biochemical CCR1 assay); Shows weak activity in the PDSP scan: The closest off-target is SLC6A4 (SERT) (Ki = 1460.83 nM) |