Selectivity of CYM-5442 for the cloned human S1P receptors
In agonist format, CYM-5442 was tested in 12-point (up to 10 μM) concentration response curves. In antagonist format, CYM-5442 was included in the assay at 10 μM final concentration and tested for its potential to block an EC80 concentration of S1P.
Receptor Subtype | Agonist Format (Emax/EC50) | Antagonist Format (IC50) |
|---|---|---|
| S1P1a | 100%/1.35 ± 0.25 nM | N.A. |
| S1P2b | N.A. | N.A. |
| S1P3c | N.A. | N.A. |
| S1P4d | N.A. | N.D. |
| S1P5e | 20% at 10 μM | N.D. |
N.A., no activity; N.D., not determined
↵ a Agonist format measured forskolin-stimulated CYM-5442 inhibiton of cAMP CRE transcription on stable S1P1-CHO-K1-CRE-bla cells, with SEW2871 as positive control. W146 inhibition of SEW2871 was used as a positive control in the antagonist format.
↵ b Agonist format measured CYM-5442-stimulated cAMP accumulation on stable CHO-K1-S1P2-CRE cells with S1P as positive control. JTE-013 (Cayman Chemical, Ann Arbor, MI) inhibition of S1P was used as positive control in antagonist format.
↵ c Agonist format measured CYM-5442-stimulated cAMP accumulation in stable S1P3-nuclear factor of activated T cells-bla-CHO-K1 cells with S1P as positive control.
↵ d Agonist format measured CYM-5442-stimulated β-arrestin activation in stable Tango S1P4-bla U2OS cells with S1P as positive control.
↵ e Agonist format measured CYM-5442-stimulated cAMP accumulation in stable Tango S1P5-bla U2OS cells with S1P as positive control.