(R)-Roscovitine

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Chemical Structure| 186692-46-6 同义名 : CYC202;Seliciclib;Roscovitin;R-roscovitine;Roscovitine
CAS号 : 186692-46-6
货号 : A300507
分子式 : C19H26N6O
纯度 : 99%+
分子量 : 354.449
MDL号 : MFCD02266401
存储条件：

Pure form Keep in dark place,Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(296.23 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 5% DMSO+2% Tween80+40% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • CDK5

    CDK5/p35, IC50:0.16 μM

  • CDK2

    CDK2/CyclinA, IC50:0.7 μM

    CDK2/CyclinE, IC50:0.7 μM

  • Cdc

    Cdc2/CyclinB, IC50:0.65 μM
描述 The CDKs (cyclin dependent kinases), as direct regulators of specific phases of the cell cycle, can control cellular proliferation and transcription with their activating cyclin partners and subunit inhibitors. Roscovitine (Seliciclib, CYC202) is a CDK2 and CDK5 inhibitor with IC50 values of 0.65, 0.7, 0.7 and 0.16 μM for cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p35 (measured by purified kinases activity), respectively. Roscovitine had a very limited effect on the cdk4/cyclin D1 and cdk6/cyclin D2 kinases (IC50 values >100 μM)[1]. It also exhibited the potency to CDK7/cyclin H with IC50 value of 0.49 μM. Roscovitine showed anti-growth effect against a panel of human tumor cell lines in cell culture, including A549, CHAGO-K1, NCI-H69, NCI-H460, LOVO, HCT15, HCT116, HT29, A498, ACHN, HT1376, MCF7, MDAMB435S, AN3CA, MES-SA, MES-SA/Dx5 and HepG2 cell lines, with IC50 values ranging from 7.9 - 30.2 μM for 72h[2]. Treatment of 60 μM roscovitine for 48h could inhibit the growth of L1210 cells and arrest cells in G2M[1]. Lovo xenografted mice treated with roscovitine, 100 mg/kg intraperitoneally 3 times daily at 8 hourly intervals for 5 days, exhibited a statistically significant reduction of 44.8% in tumor growth[2]. Phase 2 studies of roscovitine treatment for cystic fibrosis and Cushing’s Disease, and phase 1 study of roscovitine combined with sapacitabine treatment for advanced solid tumors are recruiting now (see https://www.clinicaltrials.gov/).
作用机制 Roscovitine behaves as a competitive inhibitor for ATP binding to cdc2.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=12.6007 μM SANGER
A101D Growth Inhibition Assay IC50=18.3208 μM SANGER
A3-KAW Growth Inhibition Assay IC50=5.76116 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00372073 Non-small Cell Lung Cancer Phase 2 Terminated March 2012 United States, Arizona ... 展开 >> Arizona Cancer Center Tucson, Arizona, United States, 85724 United States, California Pacific Coast Hematology Oncology Group Fountain Valley, California, United States, 92708 United States, Florida Pasco Hernando Oncology New Port Richey, Florida, United States, 34652 United States, Illinois Rush University Medical Center Chicago, Illinois, United States, 60612 The University of Chicago Chicago, Illinois, United States, 60637 United States, Maryland University of Maryland, Greenebaun Cancer Center Baltimore, Maryland, United States, 21201 United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Nebraska Nebraska Medical Center Omaha, Nebraska, United States, 68198 United States, Nevada Nevada Cancer Research Foundation Las Vegas, Nevada, United States, 89106 VA Sierra Nevada Health Care System Reno, Nevada, United States, 89502 United States, New Mexico New Mexico Oncology Hematology Consultants Albuquerque, New Mexico, United States, 87109 United States, New York Columbia Presbyterian Medical Center New York, New York, United States, 10032 United States, Pennsylvania Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania, United States, 17033 University of Pittsburg Cancer Institute Pittsburgh, Pennsylvania, United States, 15232 United States, Tennessee The Family Cancer Center Collierville, Tennessee, United States, 38017 Vanderbilt University Medical Center Nashville, Tennessee, United States, 37232 United States, Texas Southwest Regional Cancer Center Austin, Texas, United States, 78705 Center for Oncology Research and Treatment Dallas, Texas, United States, 75230 East Texas Medical Center Tyler, Texas, United States, 75701 United States, Virginia Danville Hematology Oncology Danville, Virginia, United States, 24541 收起 <<
NCT00999401 Advanced Solid Tumors Phase 1 Unknown July 2018 United States, Massachusetts ... 展开 >> Dana Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02115 Contact: Geoffrey Shapiro, M.D.    617-632-4942       Contact: Tracy Bell, R.N.    617.632.3482       Dana Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 Contact: Sara Tolaney, M.D.    617-632-2335       Contact: Leilani Anderson, RN    617-632-3129 收起 <<
NCT01333423 Breast Cancer Phase 1 Withdrawn - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.82mL

0.56mL

0.28mL

14.11mL

2.82mL

1.41mL

28.21mL

5.64mL

2.82mL
参考文献

[1]Meijer L, Borgne A, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 1997 Jan 15;243(1-2):527-36.

[2]McClue SJ, Blake D, et al. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer. 2002 Dec 10;102(5):463-8.

[3]De Azevedo WF, Leclerc S, et al. Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem. 1997 Jan 15;243(1-2):518-26.

[4]Song H, Vita M, et al. Effect of the Cdk-inhibitor roscovitine on mouse hematopoietic progenitors in vivo and in vitro. Cancer Chemother Pharmacol. 2007 Nov;60(6):841-9. Epub 2007 Feb 22.

[5]Sallam H, Jimenez P, et al. Age-dependent pharmacokinetics and effect of roscovitine on Cdk5 and Erk1/2 in the rat brain. Pharmacol Res. 2008 Jul;58(1):32-7.