ATN-224-Bis-choline-tetrathiomolybdate-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEATN-224Cat. No.: HY-16074CAS No.: 649749-10-0Synonyms: Bis(choline)tetrathiomolybdate分式: CHMoNOS分量: 432.56作靶點(diǎn): Others作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 47 mg/mL (108

2、.66 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3118 mL 11.5591 mL 23.1182 mL5 mM 0.4624 mL 2.3118 mL 4.6236 mL10 mM 0.2312 mL 1.1559 mL 2.3118 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 ATN-224種Cu2+/Zn2+-超氧化物歧化酶 1 (SOD1)

3、抑制劑。ATN-224 作內(nèi)細(xì)胞，抑制抑制SOD1活性，IC50 為 17.53.7 nM。IC50 & Target IC50: 17.53.7 nM (SOD1, in endothelial cells) 11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 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

4、ions at concentrations up to 1 mM as determined by isothermal titrationcalorimetry. ATN-224 inhibits the proliferation of both HUVEC (IC50=1.40.3 M; n=5). ATN-224 is also ableto inhibit the activity of purified bovine SOD1 with an IC50 of 0.330.03 M after 24 hours of incubation. TheSOD1 inhibition b

5、y ATN-224 is time dependent, reaching maximal inhibition at 16 hours. ATN-224 seems toinhibit 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 17.53.7 nM. ATN-224 inhibits FGF-2-induced ERK1/2phosph

6、orylation in a dose-dependent and time-dependent manner with an IC50 between 1.25 and 2.5 M,consistent with the IC50 for the inhibition of proliferation 1. ATN-224 is an orally-available inorganic smallmolecule that inhibits the copper/zinc-dependent enzyme, superoxide dismutase 1 (Cu/Zn-SOD1), inen

7、dothelial and tumor cells 2.體內(nèi)研究 ATN-224 also significantly (P 1.PROTOCOLKinase Assay 1 Cells are plated in a six-well format (100-300,000 per well) and incubated with ATN-224 at indicatedconcentrations and for indicated times. Cells are then stimulated with 10 ng/mL FGF-2 for various times andlysed

8、. Lysates are subjected to Western blot analysis using an antibody specific for phosphorylated p44/42mitogen-activated protein kinase (Thr202/Tyr204) with appropriate signal correction using an antibodyspecific for p44/42 mitogen-activated protein kinase 1.MCE has not independently confirmed the acc

9、uracy of these methods. They are for reference only.Cell Assay 1 Human umbilical vein endothelial cells (HUVEC) are maintained in M200/LSGS medium and cells are usedbetween passages 2 and 4 for all experiments. For proliferation assay, cells are plated at 3,000 per well on0.1% gelatin in M200/2% FBS

10、 for 4 hours and then stimulated with 2 ng/mL FGF-2 in the presence orabsence of ATN-224 up to 48 hours. HUVEC proliferation is determined using either the Alamar Blue or theMTT assay. Multiple myeloma MM1S cells are grown in RPMI 1640 with 10% fetal bovine serum and 2 mML-glutamine. HL-60 promyeloc

11、ytic leukemia cells and MOLT-4 acute myeloblastic leukemia cells are plated at400,000/mL in T-75 flasks and incubated for 48 to 96 hours for proliferation assays. MMS1 cell proliferation isdetermined using calcein AM 1.MCE has not independently confirmed the accuracy of these methods. They are for r

12、eference only.Animal Mice 1Administration 1 Cold Matrigel (500 L) is mixed with 800 ng/mL FGF-2 or 300 ng/mL VEGF and heparin (50 g/mL).Negative control plugs did not contain the proangiogenic factors. The Matrigel mixture is injected s.c. into 4-to 8-week-old female BALB/c nude mice. In some experi

13、ments, either ATN-224 (94 M) with or without Mn-TBAP (100 M) or water is added directly to the Matrigel plug in the treated and negative control groups,respectively. Alternatively, mice are treated by oral gavage either with distilled water or ATN-224 everydayfrom Monday to Friday. Animals are sacri

14、ficed and the plugs are recovered 5 days after plug injection. Theplugs are then minced and homogenized with a tissue homogenizer, and hemoglobin levels in the plugs aredetermined using Drabkins solution.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2

15、/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Anal Chem. 2018 Jan 16;90(2):1317-1324.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Juarez JC, et al. Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition ofsuperoxide 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, inpatients with biochemically recurrent hormone-nave prostate can