MSC-4381
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: human SLC16A3: Ki = 11 nM (IC50 = 77 nM) and mouse Ki = 252 nM (Fluorescence Cross Correlation Spectroscopy (FCCS)) |
| Selectivity within target family: > 30-fold | SLC16A1 (MCT1): SNU-398 (MCT1+/4-) cells (IC50 > 4 µM), SLC16A7 (MCT2) and SLC16A8 (MCT3): RT4 (MCT2+/3+) cells (IC50 = 638 nM) (600 fold) |
| Selectivity outside target family | CEREP binding, cellular and nuclear receptor functional assays (58 targets) at 10 µM: Closest hits are human HTR6 (IC50 = 4.6. µM), human AVPR1A (IC50 = 7.1 µM)No inhibition of PTGER1 (IC50 > 30 µM) or PTGER2 (IC50 > 30 µM).PDSP scan is clean except for HTR5A (Ki = 1625.17 nM) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: MDA-MB-231 (MCT4+/1-) cells lactate efflux inhibition assay: IC50 = 1 nM |
| Control compound (100 times less potent than the probe) | MSC-0516: MDA-MB-231 (MCT4+/1-) cells lactate efflux inhibition (IC50 = 506 nM) Closest off-targets in the PDSP scan are OPRD1 (Ki = 597.96 nM), GABA/PBR (Ki = 733.68 nM) and HTR6 (Ki = 1523.62 nM). |