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Application: Study and screen compounds that inhibit the binding of IL-17RA to IL-17A for drug discovery in high throughput screening (HTS) applications.
Background: IL-17 (interleukin 17) is a cytokine involved in inflammation and belongs to the pro-inflammatory cystine knot cytokine family. The IL-17 family includes IL-17A-F. It binds to the receptor IL-17R, which has three variants IL-17RA-C, in T helper 17 (Th17) cells in response to IL-23. It is also produced by macrophages, dendritic cells and δγ T cells. Activation of downstream pathways leads to the release of chemokines, which can recruit immune cells to inflammation sites, cytokines (such as IL-6 and GCSF (granulocyte colony stimulating factor)) and complement proteins. IL-17A is also involved in differentiation of CD34+ hematopoietic progenitor cells into neutrophils. Higher levels IL-17A have been linked to autoimmune disorders such as RA (rheumatoid arthritis), lupus psoriasis and asthma, transplant rejection and MS (multiple sclerosis). Inhibitors of IL-17 have been under development, as treatment options for autoimmune diseases, with the first monoclonal antibody been approved by the FDA in 2015 for the treatment of plaque psoriasis (secukinumab, sold under the commercial name of Cosentyx). The success of these drugs indicates the relevance of this cytokine in human health and disease, making it a valuable therapeutic target.
Description: The IL-17RA[Biotin]:IL-17A Inhibitor Screening Assay Kit is designed forscreening inhibitors of IL-17A:IL-17RA interaction. The IL-17RA[Biotin]-IL-17A Binding Assay Kitcomes in a convenient 96-well format, with biotin-labeled IL-17RA, purified IL-17A, streptavidinlabeledHRP, and assay buffer for 100 binding reactions. The key to this kit is the highsensitivity of detection of biotin-labeled IL-17RA by streptavidin-HRP. Only a few simple stepson a microtiter plate are required for the assay. First, IL-17A is coated on a 96-well plate. Next,IL-17RA is incubated with IL-17A on the plate. Finally, the plate is treated with streptavidin-HRPfollowed by addition of an HRP substrate to produce chemiluminescence, which can then bemeasured using a chemiluminescence reader.
Storage Stability: This assay kit will perform optimally for up to 6 months from date of receipt when the materials are stored as directed.
Uniprot: IL-17RA: Q96F46; IL-17A: Q16552
Warnings: Avoid freeze/thaw cycles.
Biosafety Level: Not applicable (BSL-1)
References: 1. Iwakura Y, et al. 2008. Immunol Rev. 226:57-79.
2. Bullens DM, et al. 2013. Clin Dev Immunol. 2013:840315.
3. Ley K, et al. 2006. Immunol Res. 34(3):229-42.
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