1、Product Data SheetTauroursodeoxycholate SodiumCat. No.: HY-19696ACAS No.: 35807-85-3分式: CHNNaOS分量: 521.69作靶點: ERK; Caspase作通路: MAPK/ERK Pathway; Stem Cell/Wnt; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 H2O : 100 mg/mL (191.68 mM; Need ultrasonic)DMSO :

2、100 mg/mL (191.68 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.9168 mL 9.5842 mL 19.1685 mL5 mM 0.3834 mL 1.9168 mL 3.8337 mL10 mM 0.1917 mL 0.9584 mL 1.9168 mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使，-

3、20C 儲存時，請在 1 個內使。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.79 mM); Clear solution此案可獲

4、得 2.5 mg/mL (4.79 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.79 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (4.79 mM，飽和度未知) 的

5、澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.79 mM); Clear solution此案可獲得 2.5 mg/mL (4.79 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性

6、 Tauroursodeoxycholate Sodium種內質應激抑制劑。Tauroursodeoxycholate 顯著降低凋亡分如 caspase-3 和caspase-12 表達。Tauroursodeoxycholate 也抑制 ERK。IC & Target ERK Caspase-3 Caspase-12體外研究 Tauroursodeoxycholate (TUDCA) suppresses both viability and migration of vascular smooth muscle cells (VSMCs)through inhibition of ERK

7、phosphorylation, by induction of mitogen-activated protein kinase phosphatase-1 (MKP-1)via PKC. Tauroursodeoxycholate inhibits both the proliferation and migration of VSMCs via inhibition of ERK,through Ca2+-dependent PKC translocation. Tauroursodeoxycholate prevents platelet-derived growth factor (

8、PDGF)and vascular injury-induced MMP-9 expression. The knock-down of MKP-1 using specific si-RNA restores the reducedVSMC viability by Tauroursodeoxycholate (200 M), which suggests that anti-proliferative effect ofTauroursodeoxycholate depended on the MKP-1 expression1.體內研究 The effects of Tauroursod

9、eoxycholate (TUDCA) on proliferation and apoptosis of VSMCs in vivo are examined usingimmunohistochemistry for proliferating cell nuclear antigen (PCNA) and the transferase dUTP nick-end labelling (TUNEL) assay. Tauroursodeoxycholate (10, 50, and 100 mg/kg) increases the caspase 3 activity of injure

10、d tissues in adose-dependent manner, indicating that Tauroursodeoxycholate induces apoptosis of VSMCs in the neointima. Usingthe injured tissues, further examination and comparison of the phosphorylation level of ERK and MMP-9 expression isperformed at 1 week after injury, compared with normal contr

11、ols. Balloon injury increased both the phosphorylationof ERK and expression of MMP-9 in the tissues. Tauroursodeoxycholate (10, 50, and 100 mg/kg) inhibitsphosphorylation of ERK and MMP-9 expression in a dose-dependent manner1. Tauroursodeoxycholate (TUDCA) is ahydrophilic bile acid. Tauroursodeoxyc

12、holate as a cytoprotective agent improves liver function and can preventhepatocellular carcinoma by reducing ER stress and apoptosis. Tauroursodeoxycholate significantly reducesexpression of apoptosis molecules, such as caspase-3, caspase-12, C/EBP homologous protein, c-Jun N-terminalkinase (JNK), a

13、ctivating transcription factor 4 (ATF4), X-box binding protein (XBP), and eukaryotic initiation factor 2 (eIF2) in Ang II induced ApoE-/- mice (p0.05) and total cholesterol levels (663.688.7 mg/dL vs 655.765.4 mg/dL; p0 .05) donot differ between the AAA model group and Tauroursodeoxycholate group. I

14、n addition, maximum aortic diameter issignificantly smaller in those in Tauroursodeoxycholate group compared with those in the AAA model group(0.950.03 mm vs 1.790.04 mm; p0.05). AAA lesion areas are also smaller in those in Tauroursodeoxycholate groupthan in those in the AAA model group (0.370.03 m

15、m2 vs 1.510.06 mm2; p0.05)2.PROTOCOLCell Assay 1 Cell viability and proliferation are measured using Ez-Cytox. VSMCs (5103 cells) are seeded onto 96-well plates inPage 2 of 3 www.MedChemESmooth Muscle Cell Growth Medium 2 (SMCGM2) and cultured. After serum starvation, Tauroursodeoxycholate (0,50, 10

16、0, and 200 M) is added to the hVSMCs, with or without 1,2-bis(o-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA, 10 M) and 7-hydroxystaurosporine (H7, 10 M) and cultured for24 h. To assess the effect of Tauroursodeoxycholate on the PDGF-stimulated hVSMC proliferation,

17、 hVSMCs areseeded onto 96-well plates and cultured. After serum starvation, Tauroursodeoxycholate (0, 50, 100, and 200 M) isadded to the hVSMCs, with or without PDGF-BB (50 ng/mL) and cultured. After addition of 10 L of Ez-Cytox intoeach well, cell viability is evaluated by measuring the optical den

18、sity at 450 nm1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats1Administration 12 Sprague-Dawley rats are anaesthetized with a combined anaesthetic (Ketamine, 70 mg/kg; Xylazine, 7 mg/kg ip).Tauroursodeoxycholate is administered orally once

19、a day, in different concentrations (i.e. vehicle, 10, 50, and 100mg/kg) for 2 weeks. The carotid arteries are fixed by perfusion with 4% formaldehyde, then the tissues are embeddedin paraffin, and sections (8 m) are stained with H&E1.Mice2Thirty ApoE-/- C57BL/6 male mice aged 8 weeks are randomly di

20、vided into three groups (n=10 in each group): (i)sham operated and injected with physiologic (0.9%) saline as vehicle (normal: group); (ii) mini-osmotic pumps areimplanted subcutaneously into the right flank of ApoE-/- mice to release Ang II (1000 ng/kg/min) over the course of28 days (AAA model grou

21、p); (iii) AAA model mice treated with Tauroursodeoxycholate daily for 4 weeks at a dosageof 0.5 g/kg/day in drinking water (Tauroursodeoxycholate group). Mice are sacrificed after 28 days of Ang II infusion2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 Br J Pharmacol. 2019 Jul;176(13):2162-2178. Cancers (Basel). 2020 Mar 6;12(3). pii: E613. Cell Death Dis. 2020 Apr 24;11(4):279. Front Cell Dev Biol. 2020 May. Biochem Pharmacol. 2018 May 24;154:278-292.Se