ATN-224_product_DataBase

Bioactivity

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.

Target

IC50: 17.5±3.7 nM (SOD1, in endothelial cells)

Invitro

ATN-224 has a specific and high affinity for copper ions (108 mol/L-1) and shows no binding to calcium, iron, magnesium, zinc, or manganese ions at concentrations up to 1 mM as determined by isothermal titration calorimetry. ATN-224 inhibits the proliferation of both HUVEC (IC50=1.4±0.3 μM; n=5). ATN-224 is also able to inhibit the activity of purified bovine SOD1 with an IC50 of 0.33±0.03 μM after 24 hours of incubation. The SOD1 inhibition by ATN-224 is time dependent, reaching maximal inhibition at ~16 hours. ATN-224 seems to inhibit SOD1 by depleting the enzyme of copper. ATN-224 is able to inhibit SOD1 activity in endothelial cells, an effect that is dose dependent with an IC50 of 17.5±3.7 nM. ATN-224 inhibits FGF-2-induced ERK1/2 phosphorylation in a dose-dependent and time-dependent manner with an IC50 between 1.25 and 2.5 μM, consistent with the IC50 for the inhibition of proliferation[1]. ATN-224 is an orally-available inorganic small molecule that inhibits the copper/zinc-dependent enzyme, superoxide dismutase 1 (Cu/Zn-SOD1), in endothelial and tumor cells[2]. 0 --> ATN-224 相关抗体:

In Vivo

ATN-224 also significantly (P<0.05) inhibits angiogenesis in the Matrigel plug model in mice either when added directly to the plug or when given by oral gavage. Inhibition of angiogenesis when ATN-224 is given by oral gavage occurred before there is measurable depletion of copper in either plasma or copper from the Matrigel plug. This result shows that ATN-224 inhibits angiogenesis independently of copper depletion[1].

Name

ATN-224

CAS

649749-10-0

Formula

C10H28MoN2O2S4

Molar Mass

432.56

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[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. [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.

PeptideDB

ATN-224

CAS: 649749-10-0 F: C10H28MoN2O2S4 W: 432.56