Table 2. IC50 in Human, Murine, and Rat sEH, Microsomal Stability, Solubility, and Permeability Values of the t-AUCB Related Compounds.
| permeability (Caco-2) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| sEH IC50 (nM)a |
Papp (nm/s) |
||||||||||
| Cpd | human | murine | rat | microsomal stabilityb (h/m/r) | solubilityc (μM) | A→B | B→A | ERd | LD50e(μM) | IC50 hLOX-5f(μM) | IC50 hCOX-2g(μM) |
| 4, t-AUCB | 0.5 | 1.7 | 8.0h | 94/92/46 | 25 | 1.9 | 210.3 | 111 | NDi | ND | ND |
| 20 | 0.9 | 9.9 | 0.4 | 70/10/2 | 4 | 10 | 123.7 | 12.4 | >100 | >100 | >10 |
| 22 | 0.4 | 0.4 | 0.4 | 89/29/52 | 13 | 21.5 | 46.6 | 2.1 | >100 | >100 | >10 |
| 23 | 0.5 | 0.5 | 0.4 | 77/36/60 | 7 | 0.9 | 219.1 | 243.9 | >100 | >100 | >10 |
Reported IC50 values are the average of three replicates. The fluorescent assay as performed here has a standard error between 10 and 20%, suggesting that differences of twofold or greater are significant. Because of the limitations of the assay, it is difficult to distinguish among potencies <0.5 Nm.16
Percentage of remaining compound after 60 min of incubation with human, mice, and rat microsomes obtained from Tebu–Xenotech in the presence of NADP at 37 °C.
Solubility in a 1% DMSO: 99% PBS buffer solution, see the Experimental Section for details.
The efflux ratio was calculated as ER = (Papp B → A)/(Papp A → B). See the Experimental Section for further details.
sEHI cytotoxicity tested by propidium iodide staining after 24 h of incubation in SH-SY5Y cells. See the Experimental Section for further details.
IC50 in human LOX-5 (hLOX-5). See the Experimental Section for further details.
IC50 in human COX-2 (hCOX-2) performed by Eurofins (catalogue reference 4186).
Taken from ref (24).
ND: Not determined.