Org 38286

Org 38286 is a small molecule selective glucocorticoid receptor modulator (SEGRM), also known as a dissociated glucocorticoid receptor agonist (DIGRA). Developed by Organon (now part of Merck), it was designed to treat inflammatory conditions like rheumatoid arthritis with an improved safety profile compared to traditional corticosteroids. The drug's mechanism focuses on 'dissociation,' where it selectively triggers the transrepression of pro-inflammatory genes (mediated by NF-κB and AP-1) while minimizing the transactivation of genes involved in metabolic side effects, such as those leading to osteoporosis and glucose intolerance. Although it progressed to Phase 1 clinical trials to evaluate safety and pharmacokinetics in healthy volunteers and rheumatoid arthritis patients, the development program was ultimately discontinued.