TAK-828

TAK-828 is a potent and selective orally available small molecule inverse agonist of the retinoic acid receptor-related orphan receptor gamma t (RORγt), also known as nuclear receptor subfamily 1 group F member 3. Developed by Takeda, TAK-828 was investigated primarily for immune-mediated diseases such as Crohn's disease and inflammatory bowel disease (IBD). The drug acts by inhibiting RORγt activity, thereby reducing the differentiation and activation of Th17 and Th1/17 cells—key drivers in autoimmune inflammation. Preclinical studies demonstrated that TAK-828F (a related form) reduced Th17-dependent inflammation in models of colitis and experimental autoimmune encephalomyelitis. Despite promising preclinical results, clinical development was discontinued after Phase 1 trials due to findings from preclinical toxicology and teratogenicity studies[1][2][4][5][6].