Table 3.
Sphingosine-1-phosphate receptor (S1PR) modulators in ongoing clinical trials for multiple sclerosis (MS) treatment. Features: receptor affinity, half-life (t1/2), time to reach the highest plasma concentration (Tmax), required phosphorylation, and indication for multiple sclerosis (MS) treatment (relapsing-remitting MS (RRMS)).
| Compound | Receptor Affinity | T1/2 (Hours) |
Tmax (Hours) |
Pro-Drug (Phosphorylation) |
Indication | References | |
|---|---|---|---|---|---|---|---|
| High | Low | ||||||
|
Ponesimod (ACT-128800) Actelion© |
S1PR1 (EC50 = 5.7 nM) S1PR5 (EC50 = 11 nM) |
S1PR2 (EC50 > 10,000 nM) S1PR3 (EC50 > 10,000 nM) S1PR4 (EC50 > 7000 nM) |
21–33 | 2–4 | - | RRMS (phase III) |
[159] |
|
Ceralifimod (ONO-4641) Ono Pharmaceutical© |
S1PR1 (EC50 = 0.273 nM) S1PR5 (EC50 = 0.334 nM) |
S1PR2 (EC50 > 30,000 nM) S1PR3 (EC50 > 30,000 nM) |
82–89 | 4–6 | - | RRMS (phase II) |
[160,161] |
|
Amiselimod (MT-1303) Mitsubishi tanabe pharma corporation© |
S1PR1 (EC50 = 0.075 nM) S1PR5 (EC50 = 0.47 nM) S1PR4 (EC50 = 122 nM) |
S1PR2 (EC50 > 10,000 nM) S1PR3 (EC50 > 10,000 nM) |
408 | 12–16 | + | RRMS (phase II) |
[162,163] |
|
GSK2018682 GlaxoSmithKline© |
S1PR1 (EC50 = 0.07 nM) S1PR5 (EC50 = 0.072 nM) |
S1PR3 (EC50 > 1000 nM) | 48–63 | 4–9 | - | RRMS (phase I) |
[164] |
|
CS-0777 Daiichi Sankyo© |
S1PR1 (EC50 = 1.1 nM) S1PR5 (EC50 = 21 nM) |
S1PR3 (EC50 = 350 nM) S1PR4 (no data) |
9–11 | 8–10 | + | MS (phase I) |
[165] |