. Author manuscript; available in PMC: 2013 Jan 1.

Published in final edited form as: Trends Cell Biol. 2011 Oct 14;22(1):50–60. doi: 10.1016/j.tcb.2011.09.003

Table 1.

Small molecules targeting S1P.

Name	Mechanism	Diseases	References
FTY720 (Fingolimod, Gilenya) 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol	• Prodrug; phosphorylated by SphK2	• FDA approved for multiple sclerosis^*	[15]
	• S1PR1, S1PR3–5 agonist	• Dermatitis	[82]
	• Downregulates S1P1	• Arthritis	[83]
		• Allergy	[84]

SK1-I (BML-258) (2R,3S,4E)-N-methyl-5-(4′-pentylphenyl)-2-aminopent-4-ene-1,3-diol	• SphK1 inhibitor	• Glioblastoma	[51]
		• Leukemia	[50]

Safingol L-threo-dihydrosphingosine	• pan SphK inhibitor	• Solid tumors^* (Phase 1)	[49]

SKI 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole	• SphK1 inhibitor	• Pancreatic cancer	[85]
	• Induces proteasomal and lysosomal degradation of SphK1	• Leukemia	[86]
		• Asthma	[87]

ABC294640 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridinyl-4-methyl) amide	• SphK2 inhibitor	• Cancer	[59]
	• Estrogen receptor agonist	• Rheumatoid arthritis	[88]
		• Inflammatory bowel disease	[89]

ABC294735 3-(4-chlorophenyl)adamantane-1-carboxylic acid [2-(3,4-dihydroxyphenyl)ethyl]amide	• pan SphK inhibitor	• Cancer	[90]

SKI-II (SKI-2, SPHK I₂) 4-[4-(4-chlorophenyl)-thiazolyl-2-amino]-phenol	• SphK1 inhibitor	• Asthma	[91]

THI 2-acetyl-4(5)-[1(R),2(S),3(R),4-tetrahydroxybutyl]-imidazole	• S1P Lyase inhibitor	• Ischemia/reperfusion injury	[92]
		• Lung injury	[93]

LX2931 (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime	• S1P Lyase inhibitor	• Rheumatoid arthritis^* (Phase II)	[32]

5c 2,2-dimethyl-4S-(1-oxo-2-hexadecyn-1-yl)-1,1-dimethylethyl ester-3-oxazolidinecarboxylic acid	• SphK1 inhibitor	• Sepsis	[39]

SEW2871 5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazole	• S1PR1 agonist	• Diabetic nephropathy	[94]
		• Renal protection	[95]
		• Emphysema	[96]
		• Neuroprotection	[97]
		• Spontaneous autoimmune polyneuropathy	[98]

AAL(R) 2-amino-4-(4-heptyloxyphenyl)-2-methylbutanol	• Prodrug; phosphorylated by SphK2	• Influenza	[99]
AAL(R) 2-amino-4-(4-heptyloxyphenyl)-2-methylbutanol	• S1PR1/S1PR3 agonist

AUY954	• S1PR1 agonist	• Sepsis	[100]
		• Transplanation	[101]
		• Experimental autoimmune neuritis	[102]

JTE013	• S1PR2 antagonist	• Anaphylaxis	[103]
		• Atherosclerosis	[65]
		• Cancer	[45]

Effects in humans. All other compounds have only been tested in animal models.