TABLE 2.
[35S]-GTPγS binding potencies for human S1P1–S1P5.
| Compound | Human S1P1 | Human S1P2 | Human S1P3 | Human S1P4 | Human S1P5 | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (nM) | IA (%) | EC50 (nM) | IA (%) | EC50 (nM) | IA (%) | EC50 (nM) | IA (%) | EC50 (nM) | IA (%) | |
| Ozanimod | 0.4 ± 0.03 | 85 ± 1 | >10000 | 34.8 ± 1 | >1111 | 89.4 ± 7.4 | 1486.6 ± 306.5 | 39.4 ± 5.3 | 5.84 ± 0.51 | 97 ± 3.7 |
| FTY720-p | 0.2 ± 0.01 | 84.9 ± 2.3 | >1000 | 33.2 ± 1 | 1.33 ± 0.19 | 106.5 ± 8.3 | 2.06 ± 0.3 | 59.2 ± 5.4 | 0.49 ± 0.07 | 74 ± 5.1 |
| Amiselimod-p | 0.15 ± 0.01 | 84.1 ± 1.6 | >4000 | NR | 18.98 ± 2.98 | 29.1 ± 1.6 | 2.23 ± 0.13 | 122.2 ± 3.6 | 0.58 ± 0.08 | 76.6 ± 6.9 |
| Ponesimod | 3.42 ± 1.17 | 85.8 ± 6.2 | >10000 | NR | 89.52 ± 14.29 | 82.1 ± 7.5 | >10000 | 26.5 ± 2.5 | 43.18 ± 11.99 | 92.9 ± 9.8 |
| Siponimod | 0.46 ± 0.05 | 82.1 ± 0.9 | >10000 | NR | >1111 | 90.7 ± 2.5 | 383.73 ± 67.82 | 81.5 ± 2.4 | 0.3 ± 0.02 | 102 ± 9.1 |
| KRP-203-p | 0.26 ± 0 | 85.7 ± 3.6 | >10000 | NR | 3.17 ± 0.26 | 25.7 ± 3.8 | 3.13 ± 0.29 | 56.3 ± 3.8 | 0.69 ± 0.19 | 45.8 ± 7.6 |
| Etrasimod | 5.48 ± 0.46 | 86.6 ± 1.1 | >10000 | NR | 1164.3 ± 354.1 | 81.2 ± 17 | 1125.2 ± 188.9 | 40.4 ± 4.6 | 58.87 ± 6.75 | 82 ± 4.4 |
[35S]-GTPγS binding in response to increasing concentrations of test compound performed using Chinese hamster ovary cell membranes stably expressing recombinant human S1P1–S1P5. Data shown are the mean ± standard error of the mean of the compound potencies as determined by the concentration required to elicit a half-maximal response (EC50) as well as the intrinsic activity (IA) relative to the maximal response generated with the endogenous ligand, S1P, which was taken to be 100%, calculated for 3–5 replicate experiments run in duplicate wells. NR indicates no response where the maximal response was less than 10% of that of S1P. Italic type indicates that the response was achieved at the top test compound concentration of 10000 nM, where no clear maximal response was defined.
[35S]-GTPγS, [35S]-guanosine-5'-(γ-thio)-triphosphate; S1P, sphingosine 1-phosphate; S1P1–S1P5, sphingosine 1-phosphate receptor subtypes 1 through 5.