Anti-IL-17R Antibody (Brodalumab)

Brodalumab, also known as AMG 827, is a human IgG2 anti-interleukin-17-receptor monoclonal antibody that can be used for the research of moderate-to-severe plaque psoriasis and rheumatoid arthritis (RA). IL-17A, originally known as CTLA-8 (cytotoxic T lymphocyte-associated antigen 8), is a cytokine crucial in infection and inflammatory processes. It is the most studied of the IL-17 family, which consists of six structurally related proteins: IL-17A to IL-17F. It is produced in macrophages, dendritic cells, and gammadelta-T cells. It signals via the IL-17R (IL-17 receptor) family of proteins, which includes the subunits IL-17RA-E, and are single-pass transmembrane receptors. Signaling occurs via a heterodimeric receptor typically composed of IL-17RA and a second chain. Upon binding of IL-17 to the receptor, Act1 (Act 1 adaptor protein) is activated and TRAF6 (TNF receptor associated factor 6) is recruited. Ubiquitinated TRAF6 leads to the expression of inflammatory related genes, via the NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. IL-17 dysregulation can result in psoriasis and other auto-immune disorders. The use of monoclonal antibodies able to block IL-17R have proved beneficial in the treatment of plaque psoriasis and rheumatic disorders, and bimekizumab, brodalumab, secukinumab and ixekizumab are already approved by the FDA. Brodalumab, sold under the brand name Siliq or Kyntheum, has been approved for the treatment plaque psoriasis.