Seliciclib-Roscovitine-DataSheet-生命科学试剂-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作靶点: CDK作通路: Cell Cycle/DNA Damage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

2、 : 100 mg/mL (282.13 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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，并请注意储备液的保存式和期限。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，配制前请先配制澄清的储备液，再

3、依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.05 mM); Clear solution2. 请依序添加每种溶剂： 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 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Seliciclib (Roscovitine)是有效，选择性的 CDKs 抑制剂，抑制 CDK5，CDK2 和 CDK2 的 IC50 分别为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)体外研究 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.体内

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 您边的抑制剂师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.户使本产品发表的科研献 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