Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.

ABSTRACT: Human thioredoxin-1 (TRX) is a target-selective disulfide reductase with antioxidant, anti-inflammatory, and regulatory functions that mitigates cellular stresses in various organ systems, providing a compelling rationale for therapeutic use as a broad-spectrum cell protectant. However, clinical application of recombinant TRX (rhTRX) is constrained by rapid clearance and proliferative intracellular activity. To overcome these limitations, a rationally designed TRX variant, ORP100S, was engineered for enhanced stability, prolonged extracellular target engagement, and improved protective function, with development of novel single-turnover insulin reduction and hybrid-immunocapture LC-MS assays. ORP100S demonstrates high-yield expression in E. coli (16 g L^-1) and exhibits significa

SUBMITTER: Wu J 

PROVIDER: S-EPMC12622487 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature