D9

TrxR inhibitor D9 is a potent and selective inhibitor of thioredoxin reductase (TrxR), with an EC50 of 2.8 nM. TrxR inhibitor D9 has the capability to inhibit tumor proliferation both in vitro and in vivo[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

EC50: 2.8 nM (TrxR)[1]

TrxR inhibitor D9 (0.1-1 μM; 72 h) inhibits the cell proliferation with IC50s of 0.03 and 0.1 μM for MCF-7 and HT-29 cells, respectively[1]. TrxR inhibitor D9 (72 h) completely inhibits all cancer cells (A549, KB, MDA MB-231, HeLa, MCF-7 and HT-29) viability at the concentration of 0.60 μM, and the IC50s of all cancer cells could be as low as 0.55 μM, and dose not significantly affects normal cells viability[1]. TrxR inhibitor D9 (0.8 μM; 4 and 8 h) induces HT-29 cells necrosis/apoptosis[1]. TrxR inhibitor D9 (2-20 nM; 1-60 s) inhibits TrxR activity in a concentration-dependent manner[1]. TrxR inhibitor D9 (1-1000 nM) does not significantly inhibits the catalytic activity of glutathione reductase (GR) even when the concentration increases to more than 1000 nM[1]. TrxR inhibitor D9 (0.4 μM) could effectively avoid the ligand exchange with albumin[1]. Cell Proliferation Assay[1] Cell Line: MCF-7 and HT-29 cells Concentration: 0.1, 0.5, 1 μM Incubation Time: 72 hours Result: Killed 70% MCF-7 cells and 50% HT-29 cells with the concentration as low as 0.1 μM. Apoptosis Analysis[1] Cell Line: MCF-7 cells Concentration: 0.8 μM Incubation Time: 4 and 8 hours Result: Led to more than 50% necrosis/apoptosis of cells compared to control after 4 h of treatment. Induced all cells necrosis/apoptosis after 8 h of incubation.

TrxR inhibitor D9 (5 mg/kg; i.v. once every 2 d for 15 d) effectively inhibits the growth of tumors in mice[1]. Animal Model: BALB/c nude mice (17-18 g) bearing a MCF-7 tumor[1] Dosage: 5 mg/kg Administration: I.v. once every 2 days for 15 days Result: Inhibited tumor growth with IR (inhibition ratio) of 91.5% and was well tolerated.

[1]. Zhang D, et, al. Synthesis and molecular recognition studies on small-molecule inhibitors for thioredoxin reductase. J Med Chem. 2014 Oct 9;57(19):8132-9.

[2]. Lin YX, et, al. pH-Sensitive Polymeric Nanoparticles with Gold(I) Compound Payloads Synergistically Induce Cancer Cell Death through Modulation of Autophagy. Mol Pharm. 2015 Aug 3;12(8):2869-78.