Inflammation

In vitro and mouse studies identified a RORγT inverse agonist that could help treat delayed-type hypersensitivity (DTH)-associated inflammation. Fragment-based screening, chemical synthesis of phenyl-acetamide-based analogs of the screening hit, and in vitro and cell-based activity assays yielded an inverse agonist of RORγT with IC₅₀ values of 0.6 nM in vitro and 17 nM in human cells. In a rat model of DTH-associated inflammation, oral administration of the compound decreased ear swelling and proinflammatory IL-6 levels in the ear compared with vehicle. Next steps by Novartis AG could include optimizing and testing the compound in additional animal models of DTH-associated inflammation.

Innovimmune Biotherapeutics Inc. has INV-17, a RORγT inverse agonist, in preclinical testing for uveitis, diabetes, asthma, inflammatory bowel disease, chronic obstructive pulmonary disease (COPD) and various autoimmune diseases...