Table 1.
In vitro activity of RPC1063 on the S1P receptor family compared to other S1P1 receptor agonists in clinical development
| S1P1R cAMP | S1P1R GTPγS | S1P2R GTPγS | S1P3R GTPγS | S1P4R b Β‐arrestin | S1P5R GTPγS | ||
|---|---|---|---|---|---|---|---|
| RPC1063 | EC50 (nM) | 0.16 ± 0.06 | 0.41 ± 0.16 | >10,000 | >10,000 | >7,865 ± 3697 | 11 ± 4.3 |
| Emaxa (%) | 100 | 97 | 70 | 109 | 21 | 83 | |
| FTY720‐P (Gilenya) | EC50 (nM) | 0.27 ± 0.02 | 0.27 ± 0.04 | >10,000 | 0.90 ± 0.50 | 345 ± 39 | 0.50 ± 0.08 |
| Emaxa (%) | 100 | 85 | 22 | 57 | 130 | 61 | |
| BAF312 (Siponimod) | EC50 (nM) | 0.21 ± 0.02 | 0.39 ± 0.29 | >10,000 | >10,000 | 920 ± 215 | 0.38 ± 0.09 |
| Emaxa (%) | 100 | 75 | 15 | 97 | 38 | 89 | |
| KRP203‐P | EC50 (nM) | 0.27 ± 0.10 | 0.28 ± 0.11 | >10,000 | 22 (IC50) | 11 ± 3.6 | 3 ± 1.2 |
| Emaxa (%) | 100 | N.D. | 9 | −55b | 107 | 36 |
Data represent n = 3–5 independent experiments for all receptors in all signalling pathways.
a
Emax is relative to the maximal signalling produced by S1P.
S1P1,2,3,5 receptors were assessed by GTPγS binding. S1P4 receptor activity was assessed using β‐arrestin.
b
KRP203‐P is an inverse agonist on S1P3 receptors.
N.D. = Not Determined