Publications
Leading the Way for Transformative S1P Therapies
Discover S1P Therapeutics’ industry-leading research on our cutting-edge tech and novel therapeutic pipeline.
July 2, 2024
J Medicinal Chemistry (2024)
Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile.
April 30, 2024
bioRxiv (2024)
S1P (sphingosine 1-phosphate) receptor modulator (SRM) drugs interfere with lymphocyte trafficking by downregulating lymphocyte S1P receptors. While the immunosuppressive activity of SRM drugs has proved useful in treating autoimmune diseases such as multiple sclerosis, that drug class is beset by on-target liabilities such as initial dose bradycardia.
October 11, 2023
Bioorganic & Medicinal Chemistry Letters 11, 129516 (2023)
Sphingosine-1-phosphate (S1P) is a chemotactic lipid that influences immune cell positioning. S1P concentration gradients are necessary for proper egress of lymphocytes from the thymus and secondary lymphoid tissues. This trafficking is interdicted by S1P receptor modulators, and it is expected that S1P transporter (SPNS2) inhibitors, by reshaping S1P concentration gradients, will do the same.
July 16, 2023
SLAS Discovery S2472-5552(23)00050-3 (2023)
The sphingosine-1-phosphate (S1P) pathway remains an active area of research for drug discovery because S1P modulators are effective medicine for autoimmune diseases such as multiple sclerosis and ulcerative colitis.
April 3, 2023
J Medicinal Chemistry 66, 5873-5891 (2023)
The S1P1 receptor is the target of four marketed drugs for the treatment of multiple sclerosis and ulcerative colitis. Targeting an S1P exporter, specifically SPNS2, that is “upstream” of S1P receptor engagement is an alternate strategy that might recapitulate the efficacy of S1P receptor modulators without cardiac toxicity.
August 17, 2022
Science Translational Medicine 14(658):eabj2681 (2022)
Current treatment options to slow chronic kidney disease are limited, in part due to a lack of understanding of the precise mechanisms involved with disease. Here, Tanaka et al. demonstrated that a signaling axis involving sphingosine 1-phosphate (S1P) in kidney perivascular cells resulted in increased proinflammatory cytokine production after injury in vitro and in mouse models of kidney disease.
May 24, 2022
J Medicinal Chemistry 65, 7656-7681 (2022)
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homologue 2 (SPNS2). While mouse genetic studies suggest that SPNS2 functions to maintain lymph S1P, SPNS2 inhibitors are necessary to understand its biology and to learn whether SPNS2 is a viable drug target.