TRi-1 is a potent, specific and irreversible inhibitor of cytosolic thioredoxin reductase 1 (TXNRD1), with an IC50 of 12 nM. TRi-1 has little mitochondrial toxicity for anticancer therapy[1].
in vivo
TRi-1 (10 mg/kg; i.v.; twice a day for 4 days or 5 mg/kg; i.p.; twice a week for 3 weeks) impaires growth and viability of human tumor xenografts and syngeneic mouse tumors[1].
Animal Model:
SCID mice bearing established human FaDu cell xenografts[1]
Dosage:
10 mg/kg
Administration:
Intravenous injection, twice a day for 4 days
Result:
Resulted in decreased tumor growth compared to vehicle controls within four days with no signs of overt toxicity or changes in mouse weight relative to vehicle control.
Animal Model:
PyMT-MMTV mice that spontaneously develop malignant breast cancer tumors[1]
Dosage:
5 mg/kg
Administration:
Intraperitoneal injection, twice a week for 3 weeks
[1] Stafford WC, et al. Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy. Sci Transl Med. 2018 Feb 14;10(428). pii: eaaf7444. DOI:10.1126/scitranslmed.aaf7444
