西洛多辛作用機制 - Medchemexpress - MCE中國

1、Product Data SheetSilodosinCat. No.: HY-10122CAS No.: 160970-54-7分式: CHFNO分量: 495.53作靶點: Adrenergic Receptor作通路: GPCR/G Protein; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (100.90 mM)* means soluble, but saturation unknown.Solven

2、tMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.0180 mL 10.0902 mL 20.1804 mL5 mM 0.4036 mL 2.0180 mL 4.0361 mL10 mM 0.2018 mL 1.0090 mL 2.0180 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)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(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍浮?/p>

3、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(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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(xiàn)沉淀、析出現(xiàn)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 (5.05 mM); Clear solution此案可獲得 2.5 mg/mL (5.05 mM，飽和度未知) 的澄清溶液。以 1 mL 作液

4、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(xù)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 (5.05 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.05 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

5、 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 (5.05 mM); Clear solution此案可獲得 2.5 mg/mL (5.05 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 Silodosin (KAD 3213; KMD 3213)個強效的、有選擇性的、服

6、活性的 1A-adrenergic receptor (1A-AR) 阻滯劑。Silodosin 對 1A-AR 表現(xiàn)出度的親和 (Ki=0.036 nM)， 1B-AR 和 1D-AR 親和的 162 和 50 倍，Ki 值分別為 21 nM 和 2.0 nM。Silodosin 種有效且耐受性良好的試劑，可于 LUTS/BPH 的研究。IC & Target Ki: 0.036 nM (1A-AR); 21 nM (1B-AR); 2 nM (1D-AR)1體外研究Silodosin (KAD 3213; KMD 3213) inhibits norepinephrine-induced

7、increases in intracellular Ca2+ concentrations inalpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effecton the alpha 1b- and alpha 1d-ARs1.Silodosin potently inhibits 2-2-(4-hydroxy-3-125Iiodophenyl)ethylaminomethyl-alpha-tetralone binding t

8、o thecloned human alpha 1a-AR, with a Ki value of 0.036 nM, but has 583- and 56-fold lower potency at the alpha 1b- andalpha 1d-ARs, respectively2.Silodosin (0-10 M; 24 hours) decreases ELK1 gene expression as a dose-dependent manner in all the bladder cancercell lines4.Silodosin (0-10 M; 24 hours)

9、decreases ELK1 protein expression as a as a dose-dependent manner4.Silodosin (0-10 M; 96 hours) insignificantly changes cell viability of AR-positive UMUC3 or TCCSUP cultured in anandrogen-depleted condition or that of AR-negative 647V. In contrast, silodosin reduced the growth of UMUC3 cellsculture

10、d with normal FBS containing androgens (58% decrease at 10 M)4.RT-PCR4Cell Line: TCCSUP; UMUC3 and 647V cellsConcentration: 0.1, 0.5, 3.0, or 10 MIncubation Time: 24 hoursResult: Decreases ELK1 in bladder cancer cells.Western Blot Analysis4Cell Line: TCCSUP; UMUC3 and 647V cellsConcentration: 0.1, 0

11、.5, 3.0, or 10 MIncubation Time: 24 hoursResult: Decreases ELK1 in bladder cancer cells.Cell Proliferation Assay4Page 2 of 3 www.MedChemECell Line: UMUC3,TCCSUP or AR-negative 647V cellsConcentration: 0.1, 0.5, 3.0, or 10 MIncubation Time: 96 hoursResult: Decreased cell viability of UMUC3 cells cult

12、ured with normal FBS containingandrogens (58% decrease).體內(nèi)研究 Silodosin (intravenous injection; 0.1-0.3mg/kg) reduces the obstruction-induced increases in MinP by 27.7 % (0.1mg/kg) and 20.8 %(0.3 mg/kg). It improves detrusor overactivity and reduces the grade of obstruction, and thus may be effective

13、 for both storage and voiding dysfunction for the treatment of LUTS/BPH2.Animal Model: Sprague Dawley rats2Dosage: 0.1-0.3mg/kgAdministration: Intravenous injectionResult: Effectively reduced contractions of both human and rat isolated ureters.戶使本產(chǎn)品發(fā)表的科研獻 Eur J Pharmacol. 2018 Nov 15;839:82-88.See m

14、ore customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Maxime Rossi , Silodosin in the treatment of benign prostatic hyperplasia. Drug Des Devel Ther. 2010; 4: 291297.2. Villa L, et al. Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isol

15、ated ureters.Br J Pharmacol. 2013May;169(1):230-8.3. Osman NI, et al.Silodosin : a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benignprostatic hyperplasia.Expert Opin Pharmacother. 2012 Oct;13(14):2085-96.4. Kawahara T, et al. Silodosin inhibits the growth of bladder cancer cells and enhances the cytotoxic activity of cisplatin via ELK1 inactivation.Am J CancerRes. 2015 Sep 15;5(10):2959-68. eColl