TRi-1 is irreversible inhibitor of cytosolic thioredoxin reductase 1 (TXNRD1), with an IC50 of 12 nM. TRi-1 has little mitochondrial toxicity for anticancer therapy

TRi-1, impaired growth and viability of human tumor xenografts and syngeneic mouse tumors while having little mitochondrial toxicity and being better tolerated than auranofin.

The anticancer efficacy of TRi-1 in mouse tumor models is consistent with the idea that TXNRD1 is important for cancer cell growth in vivo

Fox Chase male SCID mice were treated once with TRi-1 (0.7 to 10 mg/kg) or TRi-2 (0.5 to 20 mg/kg) via intravenous injections, and mouse health status was observed for up to 72 hours. For repeateddose toxicity studies with tumor-bearing animals, mice were first inoculated with 1*10^6 FaDu cells in phosphate-buffered saline at a preshaved region located at the anterior lateral thoracic wall . After 13 days of growth, tumors were measured by calipers, and treatments were initiated. Mice were injected with TRi-1 (10 mg/kg), TRi-2 (15 mg/kg), auranofin (10 mg/kg), or vehicle a total of nine times during a 5-day span via intravenous tail injection. Upon the final day of dosing, injections were performed subcutaneously due to hematomas in several of the mice at the tail injection site. Mouse health status was monitored daily, weight was measured, and tumor volume was recorded from caliper measurements.