Ace Therapeutics is a provider of integrated drug development services for sphingosine-1-phosphate (S1P) receptor modulators that cater to various preclinical stages of drug discovery and development. With extensive experience in G protein-coupled receptor pharmacology, we assist in designing drug candidates with optimized selectivity and potency profiles against S1P receptor 1-5 subtypes (S1PR1-5). We also provide detailed pharmacological services to characterize the potency, safety and selectivity of your candidates.
The Role of S1P Receptors in GI and Liver Diseases
S1P is a bioactive lipid that plays a crucial role in various physiological processes, including immune cell trafficking, vascular integrity, and inflammation. S1P signaling is mediated by five G-protein-coupled receptors (S1PR1-5), each exhibiting distinct tissue distribution and functions. In gastrointestinal and liver diseases, S1P receptors have garnered significant interest due to their involvement in pathophysiological mechanisms such as fibrosis, inflammation, and immune modulation. Modulation of S1P signaling pathways offers potential for the development of novel drugs targeting gastrointestinal and liver diseases.
Figure 1. Preclinical and clinical studies of S1P receptor modulators in inflammatory bowel disease (IBD). (Tourkochristou E., et al., 2023)
Types of S1P Receptor Modulators We Can Develop
We are equipped to assist in the development of modulators for all S1P receptors (S1PR1-5), including full agonists, antagonists, and partial agonists, to address a wide spectrum of GI and liver diseases.
- Selective S1PR1 Inhibitors: Reduce lymphocyte trafficking and inflammation in diseases such as IBD.
- S1PR2 Receptor Inhibitors: Alleviate cholestatic liver disease and restore intestinal flora balance.
- Partial Agonists of S1PR3: Regulate intestinal motility and inflammation.
- Multi-Targeting Approaches: Reduce lymphocytes, mucosal thickness and immune cell infiltration in IBD.
What Can We Do for the Development of S1P Receptor Modulators?
- Preclinical Efficacy Evaluation of S1P Receptor Modulators
In Vitro Efficacy Evaluation
In Vivo Efficacy Evaluation
- Cellular Models: We employ relevant cellular models of gastrointestinal and liver diseases to evaluate the efficacy of S1P receptor modulators. These may include intestinal epithelial cells, hepatocytes, stellate cells, and cancer cell lines.
- S1P Receptor Signaling Pathways: We investigate the modulation of S1P receptor signaling pathways by the tested compounds and analyze the downstream effects on cellular processes such as proliferation, migration, apoptosis, and inflammation.
We conduct preclinical studies in related animal models of gastrointestinal and liver diseases to assess the efficacy of S1P receptor modulators in reducing disease severity.
Ace Therapeutics offers a comprehensive suite of services to evaluate the safety of S1P receptor modulators. We can assess potential off-target activity, hERG channel inhibition, CYP inhibition/induction, and cytotoxicity risk of S1P candidates early in development. Our in vivo studies help assess potential toxicities, including hepatotoxicity, gastrointestinal toxicity, and off-target effects.
Our expertise encompasses the design and optimization of various formulations, including oral tablets, capsules, liquid formulations, and injectable solutions. We can also utilize advanced techniques such as nanoparticle technology to help improve the bioavailability and stability of your S1P receptor modulators.
With our expertise and comprehensive services, Ace Therapeutics is well-equipped to support and guide the development of S1P receptor modulators with therapeutic potential in gastrointestinal and liver diseases. Contact us today to discuss how our services can accelerate your S1PR modulator development program.
References
- Tourkochristou E., et al. Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases. World J Gastroenterol. 2023, 29(1):110-125.
- Liao C.Y., et al. Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. Front Immunol. 2023, 14:1130184.
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