ATN-224

Description

ATN-224 is a choline salt of tetrathiomolybdate and an inhibitor of superoxide dismutase 1 (SOD1; IC₅₀s = 2.91 and 3.51 μM in human and mouse blood cells, respectively, in vitro). ATN-224 reduces the viability of cultured oxidative stress-resistant WEHI7.2 murine thymic lymphoma cells (EC₅₀s = 5-6 nM) and human diffuse large B cell lymphoma cell lines (EC₅₀s = 9.73-105.61 nM) independently of Bcl-2 and Bcl-xL. In vivo, ATN-224 (0.7 mg/kg) chelates copper to stabilize an antitumor viral vector, enhancing its efficacy against lung metastases in mice. It also inhibits angiogenesis in a mouse model (IC₅₀s = 1.50-3 mg/kg via gavage).

Uses

ATN-224 is an oral Cu2+/Zn2+-superoxide dismutase 1 (SOD1) inhibitor. ATN-224 inhibits SOD1 activity in endothelial cells, an effect that is dose dependent with an IC50 of 17.5±3.7 nM.

in vivo

References

[1] Juarez JC, et al. Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1. Clin Cancer Res. 2006 Aug 15;12(16):4974-82. DOI:10.1158/1078-0432.CCR-06-0171
[2] Lin J, et al. A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-na?ve prostate cancer. Urol Oncol. 2013 Jul;31(5):581-8. DOI:10.1016/j.urolonc.2011.04.009