DC-9476

DC-9476 is a third-generation, highly selective small molecule inhibitor of the BRD4 protein, specifically targeting the BD2 (bromodomain 2) domain. Developed by DeepCure using an AI-driven drug discovery platform, it represents a novel class of BET (bromodomain and extra-terminal motif) inhibitors designed to address inflammation and autoimmune diseases. Unlike earlier non-selective BET inhibitors that often caused dose-limiting toxicities such as thrombocytopenia, DC-9476’s selectivity for BRD4-BD2 enables potent anti-inflammatory effects with an improved safety profile[1][3][10]. In preclinical models—including rheumatoid arthritis (RA), Still’s disease, hidradenitis suppurativa, and macrophage activation syndrome—DC-9476 demonstrated superior efficacy compared to standard-of-care therapies like TNF-alpha inhibitors (e.g., etanercept), IL-6 inhibitors, JAK inhibitors (e.g., tofacitinib), and glucocorticoids[3][4][8]. Mechanistically, it reduces key proinflammatory cytokines such as IL-17A/F, IL-1β, IL-18, IFN-gamma, TNF-alpha and IL-6 by directly inhibiting macrophage activation and modulating multiple inflammatory pathways[2][4][8]. The compound is orally administered and has shown no significant toxicity in animal studies. As of June 2025 it remains in preclinical development with plans for clinical trials.

Other names

BRD4-BD2 inhibitorBRD-4-BD2 inhibitorBRD 4-BD2 inhibitor