! The longterm goal of Apricity Therapeutics, Inc. (Apricity) is to target pharmacological transporters in the Solute Carrier superfamily (SLC) to treat diseases for which there are no available pharmacological therapies or current therapies are inadequate. SLCs are emerging drug targets because of their numerous associations in human genetic studies with a wide array of common and rare diseases. Autoimmune diseases including inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis and vitiligo are highly associated with polymorphisms in SLC genes, suggesting that SLCs play a major role in the inflammatory and abnormal immune responses that characterize these diseases. The overall goal of this SBIR Phase I proposal is to develop a platform technology for targeting SLC transporters for the treatment of autoimmune diseases with an initial focus on IBD (Crohn's disease and ulcerative colitis). In the United States, IBD is a common autoimmune disease that affects 2-3 million people. The disease involves an immune response and inflammation in the gastrointestinal tract. Genomewide association studies and knockout mice studies have provided evidence that members of several SLC families play a role in the etiology and progression of IBD as well as SLE. In this SBIR Phase I application, we propose to develop reagents that can be used to screen for small molecule inhibitors of transporters in one of the SLC families.
Two aims are proposed.
In Aim 1, stable cell lines functionally expressing each of the SLC transporters on the plasma membrane will be established and characterized.
In Aim 2, fluorescence assays for high-throughput screening will be developed and used (in up to two of the cell lines) to screen a large compound library to discover lead molecules that inhibit uptake of canonical substrates of the transporters. Follow-up studies will be performed to determine the potency and specificity of the compounds in inhibiting each of the transporters. From the proposed research, we expect to discover small molecules with different chemical scaffolds that potently and selectively inhibit these SLC transporters. This innovative project is the first to discover small molecules that target a family of SLC transporters and that can be developed as therapies for autoimmune diseases.
Autoimmune disease is a debilitating health problem worldwide as the human immune system becomes hyperactive and wreaks havoc on individuals' bodies. Unfortunately, there is no effective drug treatment for many autoimmune diseases such as inflammatory bowel disease. The research outlined here will lead to the discovery of new drugs to treat autoimmune disease.
