S1P Receptor Modulator R&D for IBD

Sphingosine-1 phosphate (S1P) is a highly biologically active lipid important in the regulation of cell survival, differentiation, migration, proliferation, immune responses, and lymphocyte trafficking, mainly through extracellular activation of the specific S1P1-S1P5 receptors. The most widely distributed is S1P1, which is a receptor which is expressed on endothelial cells and lymphocytes. The most exciting prospect, though, was the ability of S1P receptor modulators to tightly block immune cell traffic while preserving immune surveillance. Compounds that targeting S1P receptor have been successfully developed for the treatment of inflammatory bowel disease (IBD).

Fig. 1. Sphingosine-1-phosphate receptor modulators in preclinical and clinical studies in IBD. (Tourkochristou, et al., 2023)

Our S1P Receptor Modulator R&D Services

Through our remarkable network of collaborations with hundreds of pharmaceutical companies and research organizations, Ace Therapeutics assimilates years of data and knowhow, and brings all this expertise to deploy our S1P receptor modulator development services from basic sine through to preclinical evaluation.

Analysis of the Biology of S1P Metabolism and Signaling in IBD

We develop these discoveries by our analytical services that include assessment of the biology of S1P metabolism and signaling to help understand its role and mechanism in IBD. The findings are not only informative in relation to our clients' deeper knowledge of IBD pathophysiology, but also deliver valuable data to support.

• We can further investigate the impact of both the transcriptional and metabolic reprogramming of S1P metabolism on inflammation and integrity of the gut mucosal barrier by using metabolomics.
• We perform research to find out how S1P binds to selective receptors in immune cells and intestinal epithelial cells, how it regulates T and B cells activation, migration and survival and their involvement in immunity.
• We study immune-mediated inflammation of the intestine triggered by both pro-inflammatory cytokines, like IL-1β and TNF-α, via the SphK/S1P axis.
• We can study how S1P regulation modifies the migration and differentiation of leukocytes, the state of endothelial cells and their ability to interact with other immune cells in the setting of intestinal inflammation.

Types of S1P Receptor Modulators We Can Develop

We work with our clients in the discovery of S1P modulators that target S1PRs and S1P metabolism and validate their therapeutic efficacy and safety in preclinical studies by measuring their effects on lymphocyte trafficking, lymphocyte numbers, lymphocyte activity, cytokine production and intestinal barrier function in animal models of IBD.

Ace Therapeutics is committed to support our customers to develop novel S1P receptor modulators with the potential of better route of administration, pharmacokinetic features and antigenicity. Ace Therapeutics is devoted as a partner of innovative drug development in IBD, and we would like to help our customers with cost-effective manufacture of their biologics of interest. Please contact us for further information.