[1PS-058]
우수논문발표상 응모자Novel Regulation of JAK Signaling: A Nitric Oxide–Triggered Prodrug Strategy for Inflammatory Microenvironments
발표자문지민 (포항공과대학교 )
연구책임자김원종 (포항공과대학교)
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that causes progressive joint destruction. JAK inhibitors such as tofacitinib effectively suppress inflammatory signaling but can induce systemic adverse effects, including leukopenia.
Tofa-Nsc, a nitric oxide (NO)-responsive tofacitinib prodrug, was designed for inflammation-selective activation. Elevated NO levels in RA lesions were exploited as an endogenous trigger for localized drug release by introducing an o-phenylenediamine moiety.
Tofa-Nsc inhibited the JAK–STAT pathway in vitro and significantly reduced joint inflammation in a collagen-induced arthritis mouse model. Leukopenia and systemic toxicity were markedly attenuated compared with tofacitinib. NO-responsive prodrug design may improve the therapeutic index of JAK inhibition and support precision treatment of RA.