Interleukins (also abbreviated as ILs) are a kind of cytokines that is produced by and acts on a variety of cells. Interleukins are a class of cytokines with the most discovered types and the most extensive regulatory functions. At present, 38 kinds of interleukins have been found, named IL-1-IL-38 respectively. The functions of interleukins are complex and repetitive, and they play an important role in a series of processes such as the maturation, activation, proliferation and immune regulation of immune cells. Like other cytokines, the first step for interleukins to function is to bind to membrane surface receptors, the interleukin receptors (ILRs). According to their structural characteristics, the interleukin receptors can be divided into IL-17 receptors, Ig-like receptors, type I receptors and type II receptors (As the figure 1 shows).
Figure1. Four types of Interleukin Receptors
More information about Interleukins and their receptors, you can read the article entitled 'The Overview of Interleukin'. The research on the structure, function, signal transduction and genetic engineering of interleukins and their receptors is making great progress. Currently, many interleukins are being tested for clinical treatment of cancer, infectious diseases and AIDS research. Drugs targeting interleukins or their receptors include fusion proteins, antibodies and other forms. We collect several research progress of drugs targeting interleukin or interleukin receptors.
IL-1 is a polypeptide produced by monocytes, including 3 isoforms of IL-1α;, IL-1β and IL-1 receptor antagonist protein (IL-1Ra). Among them, IL-1Ra can compete with IL-1β to bind IL-1R1 and play a negative regulatory role. IL-1β is an important pro-inflammatory cytokine. After binding to receptor IL-1R1, it interacts with the coreceptor IL-1RacP to form a ternary complex of IL-1β/IL-1R1/IL-1RacP, which recruits MYD88 and activates the Intracellular NF-κB and MAPKs signaling pathways, thereby inducing the expression of a series of inflammation-related molecules, such as NLRP3. High activation of the NLRP3 inflammasome is a common feature of many inflammatory diseases, including gout, uveitis, etc. Drugs targeting the IL-1β target are very effective in these diseases. Taking canakinumab (a antibody drug targeting IL-1β) as an example, it can continuously neutralize IL-1β and inhibit the activation of NLRP3 inflammasome.
IL-17 is composed of 2 subunits to form homologous or heterodimers, subunits include IL-17A, IL-17B, IL-17C, IL-17E and IL-17F, etc., the most important of which is IL-17A and IL-17F. IL-17A has a synergistic effect with TNF-α in an arthritis model, and can induce the expression of CCL20 and promote its binding to the CCR6 in inflammatory bowel disease; IL-17A can directly act on keratinocytes and aggravate psoriasis; In addition, IL-17A is also associated with systemic lupus erythematosus, asthma and some solid tumors. IL-17F is associated with Crohn's disease (CD), psoriasis and asthma. In 2015, secukinumab developed by Novartis was approved by the FDA; in 2016, ixekizumab developed by Eli Lilly also joined the group of psoriasis treatment drugs. Both Secukinumab and ixkizumab are human antibodies targeting IL-17A. Following them, brodalumab developed by Amgen is in phase III clinical research, targeting the IL-17 receptor and can simultaneously block IL-17A, IL-17E and IL-17F signals. Its potential blocking effect and scope are greater.
CUSABIO lists partial popular targets of interleukins and interleukin receptors, click to see all the related molecules/targets and research reagents of them.
Receptor by Differentiation Cell
Receptor by Drug Target
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