ATN-224

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ATN-224（四硫代钼酸胆碱；WTX-101）是一种特异性高亲和力铜结合剂，可抑制 CuZn 超氧化物歧化酶 1 (SOD1)，IC50 为 0.33 uM。

ATN-224 (Choline tetrathiomolybdate;WTX-101) is a specific, high-affinity copper binder that inhibits CuZn superoxide dismutase 1 (SOD1) with IC50 of 0.33 uM against purified bovine SOD1, leading to antiangiogenic and antitumour effects; shows no binding to calcium, iron, magnesium, zinc, or manganese ions at 1 mM; inhibits HUVEC proliferation with IC50 1.4 uM; shows a potential therapy against Wilson's disease.Other Indication Phase 3 Clinical.

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. 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.

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.

Choline tetrathiomolybdate | WTX-101

Others

Other Targets

Other Targets

Other Indications

Other Disease

649749-10-0

432.542

C10H28MoN2O2S4

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (115.59 mM)

S=[Mo]([S-])([S-])=S.OCC[N+](C)(C)C.OCC[N+](C)(C)C

2-hydroxy-N,N,N-trimethyl-ethanaminium, tetrathioxomolybdate

(-20℃)

With Ice Pack

≥ 2 years