Sphingosine-1-phosphate (S1P) lyase catalyzes the irreversible decomposition of S1P to hexadecanaldehyde and phosphoethanolamine. 2-Acetyl-5-tetrahydroxybutyl imidazole (THI) is an inhibitor of S1P lyase.¹ Because S1P lyase is primarily expressed in lymphatic tissue, treatment of mice with THI (50 µg/ml in drinking water) increases lymphoid tissue S1P concentrations 100-fold, reducing lymphocyte egress from thymus and peripheral lymphoid organs.^1,2 The resulting lymphopenia is reversible following cessation of THI treatment.³ Reducing S1P lyase activity results in therapeutic levels of immunosuppression without the non-lymphoid lesions that result from synthetic S1P receptor agonists.⁴

1 Schwab, S.R., Pereira, J.P., Matloubian, M., et al. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309 1735-1739 (2005).

2 Gugasyan, R., Coward, A., O'Connor, L., et al. Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole. Immunology 93 398-404 (1998).

3 Bradbury, M.G., Doherty, K.V., Parish, C.R., et al. The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells. Immunology 87 80-85 (1996).

4 Vogel, P., Donoviel, M.S., Read, R., et al. Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PLoS One (2009).

Schwab, S.R., Pereira, J.P., Matloubian, M., et al. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309 1735-1739 (2005).

Bradbury, M.G., Doherty, K.V., Parish, C.R., et al. The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells. Immunology 87 80-85 (1996).

Vogel, P., Donoviel, M.S., Read, R., et al. Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PLoS One (2009).

Gugasyan, R., Coward, A., O'Connor, L., et al. Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole. Immunology 93 398-404 (1998).

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2-Acetyl-5-tetrahydroxybutyl Imidazole is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)