Seliciclib-Roscovitine-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESeliciclibCat. No.: HY-30237CAS No.: 186692-46-6Synonyms: Roscovitine; CYC202; R-roscovitine分式: CHNO分量: 354.45作靶點: CDK作通路: Cell Cycle/DNA Damage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

2、 : 100 mg/mL (282.13 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.8213 mL 14.1064 mL 28.2127 mL5 mM 0.5643 mL 2.8213 mL 5.6425 mL10 mM 0.2821 mL 1.4106 mL 2.8213 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，并請注意儲備液的保存式和期限。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?，配制前請先配制澄清的儲備液，?/p>

3、依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.05 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.05 mM); Clear solution1/3 Master of S

4、mall Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Seliciclib (Roscovitine)是有效，選擇性的 CDKs 抑制劑，抑制 CDK5，CDK2 和 CDK2 的 IC50 分別為0.2 M，0.65 M，0.7 M。IC50 & Target cdc2/cyclin B cdk2/cyclin A Cdk2/cyclin E2 CDK5/p350.65

5、M (IC50) 0.7 M (IC50) 0.7 M (IC50) 0.16 M (IC50)GST-erk1 erk1 erk2 Insulin-receptor30 M (IC50) 34 M (IC50) 14 M (IC50) tyrosine kinase70 M (IC50)體外研究 Seliciclib (Roscovitine) displays high efficiency and high selectivity towards some cyclin-dependent kinases.The kinase specificity of Seliciclib is i

6、nvestigated with 25 highly purified kinases (including protein kinase A, Gand C isoforms, myosin light-chain kinase, casein kinase 2, insulin receptor tyrosine kinase, c-src, v-abl).Most kinases are not significantly inhibited by Seliciclib (Roscovitine). Cdc2, Cdk2, and Cdk5 only aresubstantially i

7、nhibited (IC50 values of 0.65, 0.7, and 0.2 M, respectively). Cdk4k and Cdk6 are very poorlyinhibited by Seliciclib (Roscovitine) (IC50100 M). Extracellular regulated kinases erk1 and erk2 areinhibited with an IC50 of 34 M and 14 M, respectively. Seliciclib (Roscovitine) inhibits the proliferation o

8、fmammalian cell lines with an average IC50 of 16 M 1. Seliciclib decreases the level of CDK5 and p35 withupregulation of E-cadherin, but downregulation of Vimentin and Collagen IV. Moreover, Seliciclib(Roscovitine) inhibits the ability of high glucose cultured NRK52E cells to migrate and invade 2.體內(nèi)

9、研究 Compare with normal controls, Seliciclib (Roscovitine) downregulates phosphorylated ERK1/2 and PPARwith concomitant increase in E-cadherin, but decrease in Vimentin and Collagen IV. Correspondingly,Seliciclib decreases renal tubulointerstitial fibrosis of diabetic rats. Seliciclib (Roscovitine) i

10、s effective indecreasing tubulointerstitial fibrosis via the ERK1/2/PPAR pathway in diabetic rats 2. Seliciclib(Roscovitine) (16.5 mg/kg) significantly reduces the rate of tumor growth and increases survival of treatedmice. Strikingly, Seliciclib (Roscovitine) treatment leads to complete tumor disap

11、pearance in one mouse(25%); moreover, no tumor regrowth in this mouse is found 5 months after completion of the treatment.Mouse weights do not differ significantly between mice treated with Seliciclib and control mice, andbehavioral differences between the two groups are also negligible. These resul

12、ts suggest that Seliciclib canbe used effectively as a selective tumor growth inhibitor in HPV+ head and neck cancer 3.PROTOCOLCell Assay 2 Rat kidney tubular epithelial cells (NRK52E) are used. CDK5 inhibitor Seliciclib (Roscovitine) (Ros.; 10 M)and activator p35 (15 M), PPAR agonist Rosiglitazone

13、(Rosi.; 50 nM), and ERK1/2 inhibitor U0126 (50 nM)are used to treat NRK52E cells. Cells in each group are treated for 72 hours and then harvested for further2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEanalyses 2.MCE has not independently confirmed the accuracy of these methods. They are for ref

14、erence only.Animal Rats 2Administration 23 Male Sprague Dawley rats (6-8 weeks of age) are given intraperitoneally a single injection of eitherStreptozotocin (65 mg/kg) diluted in 0.1 M citrate buffer pH 4.5 (diabetic) or citrate buffer (non-diabetic).Plasma glucose concentrations are determined usi

15、ng the glucose oxidase method on a glucose analyzerthree days after the injection. Rats with a glucose level over 16.7 mM are considered diabetic and thusincluded in the study. Plasma glucose level is measured once every week. To investigate the effect of CDK5inhibition on renal tubulointerstitial f

16、ibrosis, Seliciclib (25 mg/kg) is injected peritoneally to diabetic rats everyday till sacrifice. DMSO is included as controls.Mice 3Exponentially growing UMSCC47 cells are injected subcutaneously into the sacral area of female NUDEmice. Each mouse is inoculated with 2105 cells in 50% matrigel and 5

17、0% PBS at a volume of 100 L. Aftertumors reach a measurable size, the mice are given 16.5 mg/kg doses of intraperitoneal Seliciclib or vehicleinjections. Body weight, tumor growth, and general behavior are monitored. Tumor volumes are measuredevery 3 days. Mice are sacrificed when the tumor exceeded

18、 a size of 0.5cm3.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. 2018 Jul 18;10(450). pii: eaaq1093. Cell Syst. 2018 Apr 25;6(4):424-443.e7. Neoplasia. 2018 Mar 28;20(5):478-488. Chin J Org Chem. 2017, 37. Chin J Org Chem. 2016, 36(5): 1044-1050.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Meijer L, et al. Biochemical and cellular