The nuclear hormone receptor RORγt has emerged as the “master” regulator of Th17 cell differentiation and the production of pro-inflammatory cytokines, such as IL-17A and IL-17F. Increased production of these cytokines has been linked to the pathophysiology of psoriasis. Small molecule inhibitors of RORγt have been shown to reduce production of IL-17 in immune cells and are promising therapies for psoriasis and other autoimmune conditions.
Small-molecule inhibition of RORγt has been shown to reduce production of the inflammatory cytokine IL-17, which plays a key role in autoimmune disorders. Inhibitors of RORγt are being developed for the treatment of IL-17 mediated autoimmune diseases, such as psoriasis and associated co-morbidities. RORγt inhibitors have therapeutic opportunities beyond psoriasis, such as psoriatic arthritis, rheumatoid arthritis, lupus, inflammatory bowel disease and multiple sclerosis. Small-molecule inhibitors of RORγt are also called RORγt “inverse agonists”. Data from a recent clinical trial in mild-to-moderate psoriasis patients has validated RORγt as a target for psoriasis therapy.