Table 1.

[γ-³⁵S]-GTP binding assay in HEK293T cells over-expressed with subtype specific S1P receptors.^a

			Receptors
			S1P1		S1P2		S1P3		S1P4		S1P5
Compound	linker	Head Group	EC50a	Emax	EC50	Emax	EC50	Emax	EC50	Emax	EC50	Emax
FTY720-P	H2CCH2	phosphate	1.3	1.00	NA	0.00	0.1	0.50	4.0	0.90	4.0	0.56
VPC22173	amide	phosphate	58.0	1.10	NA	0.00	450.0	0.35	500.0	1.10	52.0	0.79
VPC2301S	amide	phosphate	NA	0.00	NA	0.00	NA	0.00	120.0	1.13	480.0	0.57
12 a	amide	phosphonate	3.6	0.96	270.0	0.50	43.0	0.88	230.0	0.67	30.0	0.77
b	amide	phosphonate	27.0	0.93	NA	0.00	270.0	0.38	2,300.0	0.80	76.0	0.64
c	amide	phosphonate	NA	0.00	n/a	n/a	NA	0.00	n/a	n/a	n/a	n/a
d	amide	phosphonate	NA	0.00	NA	0.00	NA	0.00	6,100.0	1.42	33.0	0.73
6	amide	phosphonate	1200.00	NA	NA	0.00	15000	0.30	n/a	n/a	n/a	n/a
f	amide	phosphonate	NA	0.00	NA	0.00	NA	0.00	n/a	n/a	n/a	n/a
13	amide	fluorophosphonate	2.1	0.99	490.0	0.47	23.0	0.96	170.0	0.68	19.0	0.77
18 a	ether	phosphonate	68.0	0.70	NA	0.00	NA	0.00	147.0	0.71	31.0	0.41
b	ether	phosphonate	140.0	0.64	530.0	0.50	100.0	0.53	150.0	0.90	47.0	0.50
19	ether	phosphonate	33.0	0.43	NA	0.00	NA	0.00	440,000.0	0.45	NA	0.00
26	amine	phosphonate	30.0	0.56	NA	0.00	NA	0.00	340.0	1.18	41.0	0.61

^aEC₅₀s are nM and determined by the mean of at least three experiments.

Emax values are normalized to the maximal activation of endogenous S1P, at each receptor.

NA = no activation

n/a = not available