西洛多辛作用机制 - Medchemexpress - MCE中国

1、Product Data SheetSilodosinCat. No.: HY-10122CAS No.: 160970-54-7分式: CHFNO分量: 495.53作靶点: Adrenergic Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (100.90 mM)* means soluble, but saturation unknown.Solven

2、tMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。

3、以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.05 mM); Clear solution此案可获得 2.5 mg/mL (5.05 mM，饱和度未知) 的澄清溶液。以 1 mL 作液

4、为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.05 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (5.05 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO

5、 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.05 mM); Clear solution此案可获得 2.5 mg/mL (5.05 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Silodosin (KAD 3213; KMD 3213)个强效的、有选择性的、服

6、活性的 1A-adrenergic receptor (1A-AR) 阻滞剂。Silodosin 对 1A-AR 表现出度的亲和 (Ki=0.036 nM)， 1B-AR 和 1D-AR 亲和的 162 和 50 倍，Ki 值分别为 21 nM 和 2.0 nM。Silodosin 种有效且耐受性良好的试剂，可于 LUTS/BPH 的研究。IC & Target Ki: 0.036 nM (1A-AR); 21 nM (1B-AR); 2 nM (1D-AR)1体外研究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).体内研究 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.户使本产品发表的科研献 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