TABLE 2

Lymphopenic and toxic effects of compounds in mice compared with binding activity on rodent S1P receptors

ED50 values (±S.E.) are the dose (in milligrams per kilogram) that produces 50% of the maximum reduction in peripheral blood lymphocytes at 3 h. Toxicity is the maximum tolerated dose (milligrams per kilogram) as defined under Materials and Methods. Compounds were tested in vitro in [33P]S1P binding assays to determine IC50 values (nanomolar) using membranes prepared from CHO cells expressing mouse and rat S1P receptors.




S1P

A

C

D

E

F
PBL ED50 ND 0.03 (0.01) 0.32 (0.08) 0.063 (0.007) 0.7 (0.4) 2.2 (0m.8)
Toxicity 0.4 1.0 4.0 0.05 >10 >30
mS1P1 IC50 0.3 0.3 2.5 0.9 4.1 14.6
rS1P1 IC50 0.3 0.3 2.1 0.8 4.2 6.4
mS1P3 IC50 0.3 2.7 71 1.8 605 6576
rS1P3 IC50 0.3 3.1 74 2.6 825 7172
mS1P4 IC50 40 28 99 130 109 200
mS1P5 IC50
0.3
0.5
29
2.8
7.1
4.2
  • ND, not determined.