毛喉素作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetForskolinCat. No.: HY-15371CAS No.: 66575-29-9分式: CHO分量: 410.5作靶點(diǎn): Adenylate Cyclase; FXR; Autophagy作通路: GPCR/G Protein; Metabolic Enzyme/Protease; Autophagy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 : 100 mg/mL (243.61 mM; Need ultrasonic)

2、H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.4361 mL 12.1803 mL 24.3605 mL5 mM 0.4872 mL 2.4361 mL 4.8721 mL10 mM 0.2436 mL 1.2180 mL 2.4361 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；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?/p>

3、 1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.09 mM); Clear solution此案可獲得 2.5 mg/m

4、L (6.09 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(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.09 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.09 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。

5、以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Forskolin (Coleonol) 種有效的腺苷酸環(huán)化酶 (adenylate cyclas) 激活劑，對(duì)于 I 型腺苷酸環(huán)化酶，IC50 為 41 nM， EC50 為 0.5 M。Forskolin 也 種細(xì)胞內(nèi) cAMP 形成的誘導(dǎo)劑。Forskolin 誘導(dǎo)多種細(xì)胞類型的分化并激活孕烷 X 受 體 (PXR) 和 FXR。Forskolin 對(duì)臟產(chǎn)正性肌作，并具有板抗凝集和降壓作。Forskolin 也可誘導(dǎo)細(xì)胞噬 (

6、autophagy)。IC & Target IC50: 41 nM (Adenylyl cyclase)1EC50: 0.5 M (Adenylyl cyclase)1體外研究 Forskolin (Fsk) is a naturally occurring diterpene isolated from Coleus forskholii, directly activates adenylyl cyclase(AC) through its catalytic subunit to increase intracellular levels of cyclic adenosine mon

7、ophosphate (cAMP)1.Forskolin (Fsk) affects the proliferation of the human T-cell lines such as Kit 225 and MT-2. Forskolin treatmentinhibits the proliferation of both Kit 225 and MT-2 cells in a dose-dependent manner with an IC50 equal to 5 MFsk. Forskolin treatment (10-100 M) increases cAMPi levels

8、 5- to 20-fold above basal levels, which reachemaximum levels between 50-100 M Forskolin6.體內(nèi)研究 The Forskolin (Fsk)-treated Mrp4-/- mice shows an increased number of Ki67-positive and cleaved caspase 3-positiveECs, a significant decrease in the amount of pericyte coverage, and a reduced number of emp

9、ty sleeves. In pupsexposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4-/- mice shows a significant increase in theunvascularized retinal area2. The average blood glucose in the healthy rat group is 102.121.94 mg/dL, 101.253.56for control group and 1032.08 in forskolin group. The data shows th

10、at glucose levels at the end of the study arelower in forskolin group, with a significant difference according to the statistical tests applied (p=0.03)7.PROTOCOLCell Assay 2 Quiescent Kit 225 or MT-2 cells are seeded into 96-well plates at 5104 cells per well. Cells are then pretreated for 1h with

11、1% DMSO (vehicle) or Forskolin at 1, 5, 10, 25, 50, and 100 Mconcentrations. The cells are stimulated with IL-2 and cultured for an additional 20 h at 37C. Control cells are treated with 1% DMSO for 20 h. During the final 4 h ofincubation, the cells are pulsed with 3Hthymidine at a concentration of

12、0.5 Ci/200 L. Cells are harvested ontofiberglass filters and analyzed using liquid scintillation counting2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice3Administration 34 C57BL/6J mice are used. Mrp4-knockout mice, which are established an

13、d repeatedly backcrossed to the C57BL/6Jmice. Forskolin is injected intraperitoneally into neonatal mice at postnatal days 4 (P4) and 5 (P5). Mice injected withDMSO serve as the controls. The treated mice are euthanized at P6, and their retinas are isolated for whole-mountimmunohistochemistry (IHC).

14、 The effect of different concentrations of Forskolin on the survival rate and retinalvasculature is first tested, and the optimal concentration is determined, 1.0 g/50 L (0.3 mg/kg) at P4 and 1.5 g/50L (0.5 mg/kg) at P5, used to compare the retinal vascular phenotypes between WT mice and Mrp4-defici

15、ent mice.Rats4Male Wistar rats, aged 10-14 weeks old, with a mean weight of 300 g50 g, are divided into four groups; 19 areexperimentally induced to develop diabetes, and 8 are maintained in a healthy condition. Both diabetic and healthyrats receive no Forskolin (control), or 6 mg/kg per day of Fors

16、kolin, administered orally for 8 weeks. Blood glucosePage 2 of 3 www.MedChemElevels are determined in each group before and after Forskolin treatment. The diabetic rats are tested two weeks afterconfirming the presence of diabetes (three weeks after the induction) and after eight weeks of the design

17、atedtreatment.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2020 May 6;12(542). pii: eaba0769. Biomaterials. 2018 Dec 6;193:30-46. Br J Pharmacol. 2019 Aug;176(16):2962-2976. Cell Death Dis. 2020 May 26;11(5):394. J Exp Cli

18、n Cancer Res. 2019 Sep 13;38(1):404.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Robbins JD, et al. Forskolin carbamates: binding and activation studies with type I adenylyl cyclase. J Med Chem. 1996 Jul 5;39(14):2745-52.2. Rodriguez G, et al. Forskolin-inducible

19、cAMP pathway negatively regulates T-cell proliferation by uncoupling the interleukin-2 receptor complex. J BiolChem. 2013 Mar 8;288(10):7137-46.3. Matsumiya W, et al. Forskolin modifies retinal vascular development in Mrp4-knockout mice. Invest Ophthalmol Vis Sci. 2012 Dec 7;53(13):8029-35.4. Ros-Silva M, et al. Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes. Int J MedSci. 2014 Mar 11;11(5):448-52.5. Mayati A, et al. Functional polarization of human hepatoma HepaRG cells in