RX1 enables quantitative high-throughput cellular screening for TrxR1 inhibitors: Inhibitors of TrxR1 hold promise as therapeutics for treating cancer, autoimmune and inflammatory diseases. The chalcophilic gold complex auranofin (Ridaura) is one effective though poorly selective TrxR inhibitor, clinically used against the autoimmune inflammatory disease, rheumatoid arthritis. It and many analogues complexes have reached late-stage clinical trials in cancer, motivated by tumoral upregulation and reliance upon redox systems. Other TrxR inhibitor classes include redox-active species and organic electrophiles. Until now, TrxR1 assays to guide inhibitor development were enzymatic ("cell-free") or utilised cell lysates. The technical and cost challenges of expressing and purifying mTrxR with near-quantitative selenium-incorporation on a sufficient scale for large screening, have limited enzymatic TrxR screening: only one high-throughput screen (HTS) has been reported. Enzymatic or lysate assay hits can be irrelevant in cells (poor permeability, biolocalisation, or target specificity), report artifactual hits (e.g. fluorescence quenching or aggregation), and can identify promiscuous compounds that are unlikely to be useful in biology, rather than selective compounds. Biochemical assays also cannot identify compounds that are biotransformed into active inhibitors: a field that is recently emerging for selenoprotein targeting. Cellular HTS can be far simpler and cheaper to perform; and allows screening different cell lines, towards therapeutic TrxR inhibitors effective in target cells (with varied expression levels of TrxR and of likely off-target thiol / selenol species), while controlling for drug-relevant performance issues such as upregulated electrophile detoxification and drug efflux pumping, and cell-type-dependent uptake. If a selective probe/readout is used, the data can also be more likely to emphasise selectivity over nonspecific reactivity, making it more actionable in drug development. A HTS-suitable probe must be TrxR-selective; but it must also pass many additional criteria for automatic operation, including (a) broad dynamic range (negligible background and cellular crosstalk, high signal-to-noise); (b) broad linear range (for quantitative use); (c) minimal count of error-prone steps (no additional reagents or handling); (d) no manual tailoring of conditions or processing by compound classes; (e) high-quality data: stable signal, with high precision (small deviations) and high accuracy (confidence of TrxR quantification, minimum interference from test compounds) (see Supporting Information).