TRi-1

TRi-1 (CAS No.: 246020-68-8) is a class of synthetic small-molecule research probe classified as a selective and irreversible cytosolic thioredoxin reductase 1 (TXNRD1) inhibitor, suitable for functional analysis and target validation of the thioredoxin system in redox biology and oncology-focused discovery research. By covalently inhibiting the catalytic activity of TXNRD1, it limits the regeneration of thioredoxin Trx1, thereby perturbing intracellular redox homeostasis; in specific human tumor cell models, this inhibition is associated with phenotypes such as increased intracellular hydrogen peroxide levels and decreased mitochondrial oxygen consumption rate, reflecting intervention in thioredoxin-centered peroxide clearance and mitochondrial respiration processes. In in vitro enzymatic assays, TRi-1 shows low-nanomolar inhibitory activity against TXNRD1 (reported IC50 approximately 12 nM), while in cellular systems common functional responses often occur at low-micromolar levels, with overall activity summarized as being in the nanomolar to micromolar range. Chemical proteomics and comparative studies suggest that, within tested systems, its targeting selectivity for TXNRD1 is higher than that of some broader-spectrum metal-based inhibitors (such as auranofin), and therefore it can serve as a pathway-specific tool compound for dissecting thioredoxin-dependent signal transduction, oxidative stress adaptation, and metabolic coupling. Typical applications include modulating redox signaling and assessing pathway involvement in cultured cells, as well as exploring TXNRD1 dependency in animal research models such as xenografts, and it can be incorporated into biochemical or high-content screening workflows; the concentration or dose used in experiments typically depends on the specific experimental design, biological context, and readout settings, and all use scenarios are limited to life science research.