1、Product Data SheetBosentan (hydrate)Cat. No.: HY-A0013ACAS No.: 157212-55-0分式: CHNOS分量: 569.63作靶點: Endothelin Receptor作通路: GPCR/G Protein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 DMSO : 100 mg/mL (175.55 mM)Ethanol : 50 mg/mL (87.78 mM; Need ultrasonic)H2O : 0.1

2、 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.7555 mL 8.7776 mL 17.5553 mL5 mM 0.3511 mL 1.7555 mL 3.5111 mL10 mM 0.1756 mL 0.8778 mL 1.7555 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

3、。-80C 儲存時，請在 6 個內使，-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 (4.39 mM)

4、; Clear solution此案可獲得 2.5 mg/mL (4.39 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)Page 1 of 2 www.MedChemESolubility: 2.5 mg/mL (4.39 mM); Clear solution此案可獲得 2.5 mg/

5、mL (4.39 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 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.39 mM); Clear solution此案可獲得 2.5 mg/mL (4.39 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。4.

6、請依序添加每種溶劑： 10% EtOH 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.39 mM); Clear solution此案可獲得 2.5 mg/mL (4.39 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 EtOH 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。5. 請依序添加每種溶劑： 10% EtOH 90% (20% SBE-CD in saline)

7、Solubility: 2.5 mg/mL (4.39 mM); Clear solution此案可獲得 2.5 mg/mL (4.39 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 EtOH 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。BIOLOGICAL ACTIVITY物活性 Bosentan hydrate 和 95 nM。種競爭性的 endothelin-1 (ET) 拮抗劑，在SMC中，作于 ETA 和 ETB 受體，Ki 分別為 4.7 nMIC & Target Ki: 4.7 nM (ETA r

8、eceptor, in human SMC), 95 nM (ETA receptor, in human SMC)1體外研究 Bosentan (BOS) competitively and specifically antagonizes binding of 125I-labelled ET-1 to ETA receptors on humansmooth muscle cells (SMC) and ETB receptors on human placenta cells. The in vitro binding affinity of Bosentan to ETArecept

9、ors on human SMC is 4.7 nM and to ETB receptors on human SMC or placenta cells is 41 or 95 nM. Bosentanhas 67-fold greater selectivity for ETA than ETB receptors (mean IC50=7.1 vs 474.8 nM) in an in vitro 125I-labelingassay1.體內研究 Single-dose Bosentan 62.5 mg significantly (p0.01 vs baseline) plasma

10、ET-1 levels by 2-fold in 7 pts with WHO classII or III idiopathic or CTD-associated PAH, with peak levels achieved at 8 h1. In hypertensive rats, Macitentan 30mg/kg further decreases mean arterial blood pressure (MAP) by 19 mm Hg when given on top of Bosentan 100mg/kg. Conversely, Bosentan given on

11、top of Macitentan fails to induce an additional MAP decrease. In pulmonaryhypertensive rats, Macitentan 30 mg/kg further decreases mean pulmonary artery pressure (MPAP) by 4 mm Hg ontop of Bosentan, whereas a maximal effective dose of Bosentan given on top of Macitentan does not cause anyadditional

12、MPAP decrease3.PROTOCOLCell Assay 2 Cell viability is evaluated by the trypan blue exclusion test. Human dermal fibroblasts are treated with the indicatedconcentration of Bosentan (10, 20 and 40 M). Cell viability is examined at 24 and 48 hours. Stained (dead) andunstained (viable) cells are counted

13、 with a hematocytometer2.Page 2 of 3 www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats3Administration 3 Two-month-old DSS rats and two-month-old Wistar rats are used. Pharmacological effects on mean arterial pressure(MAP) or mean p

14、ulmonary arterial pressure (MPAP) and heart rate (HR) are measured up to 120 h after a singlegavage at doses ranging from 0.1 to 100 mg/kg (Macitentan) or 3 to 600 mg/kg (Bosentan). To determine whetherMacitentan can provide superior pharmacological activity vs. Bosentan, a study is designed in whic

15、h: 1) Macitentan isadministered on top of the maximal effective dose of Bosentan established by the dose-response curve. 2) the samedose of Bosentan is administered on top of the maximal effective dose of Macitentan. The maximal effective dose ofthe second compound is administered at Tmax of the fir

16、st tested compound.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 Hypertension. 2019 Dec;74(6):1409-1419. Phytomedicine. 2019 Mar 15;56:175-182. Am J Physiol Endocrinol Metab. 2019 Sep 1;317(3):E548-E558. Am J Physiol Heart Circ Physiol. 20

17、19 Oct 11. Toxicology. 2020 Apr 4:152445.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Dhillon S, et al. Bosentan: a review of its use in the management of mildly symptomatic pulmonary arterial hypertension. Am J Cardiovasc Drugs.2009;9(5):331-50.2. Akamata K, et a

18、l. Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcriptionfactor Fli1. Arthritis Res Ther. 2014 Apr 3;16(2):R86.3. Iglarz M, et al. Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmon