Roscovitine (Seliciclib,CYC202)

Catalog No.S1153
5 5 8 Product Citations

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. Phase 2.

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Roscovitine (Seliciclib,CYC202) Chemical Structure

Roscovitine (Seliciclib,CYC202) Chemical Structure
Molecular Weight: 354.45

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

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Roscovitine (Seliciclib,CYC202) is available in the following compound libraries:

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Product Information

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  • Research Area
  • Inhibition Profile
  • Roscovitine (Seliciclib,CYC202) Mechanism

Product Description

Biological Activity

Description Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. Phase 2.
Targets CDK5/p35 [1] Cdc2/CyclinB [1] CDK2/CyclinA [1] CDK2/CyclinE [1] ERK2 [1]

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IC50 0.16 μM 0.65 μM 0.7 μM 0.7 μM 14 μM
In vitro Roscovitine displays high efficiency and high selectivity towards some cyclin-dependent kinases with IC50 of 0.65, 0.7, 0.7 and 0.16 μM for cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p53, respectively. [1] Roscovitine reversibly inhibits the prophaselmetaphase transition in the micromolar range of starfish oocytes and sea urchin embryos, inhibits in vitro M-phase-promoting factor activity and in vitro DNA synthesis in Xenopus egg extracts, and suppresses the proliferation of mammalian cell lines with an average IC50 of 16 μM. [1] In mesangial cells, Roscovitine results in a dose-dependent reduction of CDK2 activity that at concentrations of 7.5, 12.5 and 25 mM, Roscovitine causes a 25, 50% and 100% decrease in CDK2 activity, respectively. [2] A recent study shows that Roscovitine inhibits cdk5 kinase activity, cell proliferation, multicellular development, and cdk5 nuclear translocation in Dictyostelium discoideum, without affecting the expression of cdk5 protein during axenic growth. [3]
In vivo Roscovitine, at a dose of 50 mg/kg, significantly inhibits growth of The Ewing's sarcoma family of tumors (ESFT) xenografts. [4] Roscovitine enhances the antitumor effect of doxorubicin without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis in nude mice bearing established MCF7 xenografts. [5]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

Enzymes Kinases activities are assayed at 30 °C in buffer C. Blank values are subtracted from the data and activities calculated as molar amount of phosphate incorporated in protein acceptor during a 10-minute incubation. Controls are performed with appropriate dilutions of DMSO. In a few cases, phosphorylation of the substrate is assessed by autoradiography after SDS/PAGE. p34cdc2/cyclin B is purified from M-phase starfish (M. glacialis) oocytes by affinity chromatography. It is assayed with 1 mg histone Hl/mL, in the presence of 15 μM [γ-32P]ATP (3000 Ci/mmol; 1 mCi/mL) in a final volume of 30 μL. After a 10-minute incubation at 30 °C, 25-μL aliquots of supernatant are spotted onto pieces of Whatman P81 phosphocellulose paper, and, after 20 seconds, the filters are washed five times (for at least 5 minutes each time) in a solution of 10mL phosphoric acid/L water. The wet filters are transferred into 6-mL plastic scintillation vials, 5 mL ACS scintillation fluid is added and the radioactivity measured in a Packard counter. The kinase activity is expressed as molar amount of phosphate incorporated in histone H1 during a 10-minutes incubation or as a percentage of maximal activity. p33cdk2/cyclin A and p33cdk2/cyclinE are reconstituted from extracts of sf9 insect cells infected with various baculoviruses. Cyclins A and E are fusion proteins with glutathione S-transferase and the complexes are purified on glutathione-agarose beads. Kinase activities are assayed with 1 mg/mL histone H1, in the presence of 15 μM [γ-32P]ATP, during 10 minutes, in a final volume of 30 μL, as described for the p34cdc2/cyclin B kinase. p33cdk5/p35 is purified from bovine brain, excluding the Mono S-chromatographic step. The active fractions from the Superose 12 column are pooled and concentrated to a final concentration of approximately 25 μg enzyme/mL. The kinase is assayed with 1 mg/mL histone HI in the presence of 15 μM [γ-32P]ATP, during 10 minutes in a final volume of 30 μL, as described for the p34cdc2/cyclin B kinase. p33cdk5/cyclin D1 is obtained from insect cell lysates. Cdk4 is a fusion protein with glutathione-S-transferase and the active complex is purified on glutathione-agarose beads. Its kinase activity is assayed with purified retinoblastoma protein (complexed with glutathione-S-transferase) in the presence of 15 μM [γ-32P]ATP, in a final volume of 30 μL. After a 15-minute incubation, 30 μL Laemmli sample buffer is added. The phosphorylated substrate is resolved by 10 % SDS/PAGE and analysed by autoradiography by overnight exposure to Hyperfilm MP and densitometry. p33cdk4/cyclinD 2 is obtained from insect cell lysates. It is assayed with purified retinoblastoma protein (complexed with glutathione-S-transferase) in the presence of 15 μM [γ-32P]ATP in a final volume of 30 μL. After a 30-minute incubation, 30 μL Laemmli sample buffer is added. The phosphorylated substrate is resolved by 10% SDS/PAGE and analysed by autoradiography by overnight exposure to Hyperfilm MP and densitometry. MAP kinase erkl (tagged with glutathione-S-transferase), is expressed in bacteria, purified on glutathione-agarose beads and assayed with 1 mg myelin basic protein/ml in the presence of 15 μM [γ-32P]ATP as described above for the p34cdc2cyclin B kinase. His-tagged erkl and erk2 are activated in vitro by mitogen-activated protein kinase kinase, purified (Ni-affinity and Mono Q) and assayed as described above during 10 minutes in a final volume of 30 μL. Protein kinase C isoforms are purified from baculovirus infected sf9 insect cells and assayed with 1 mg/mL protamine sulfate in the presence of 15 μM [γ-32P]ATP, during 10 minutes at 30 °C, in a final volume of 30 μL. Phosphorylated protamine sulfate is recovered on Whatman P81 phosphocellulose paper as described for the cdc2 kinase. The catalytic subunit of cAMP-dependent protein kinase, purified from bovine heart, is assayed with 1 mg histone Hl/ml, in the presence of 15 μM [γ-32P]ATP as described for the p34cdc2/cyclin B kinase. cGMP-dependent protein kinase, purified to homogeneity from bovine tracheal smooth muscle, is assayed with 1 mg histone Hl/mL, in the presence of 15 μM [γ-32P]ATP as described for the p34cdc2/cyclin B kinase. Casein kinase 2 is isolated from rat liver cytosol and assayed with 1 mg casein/mL and 15 μM [γ-32P]ATP. The substrate is spotted on Whatmann 3MM filters and washed with 10% (mass/vol.) trichloroacetic acid. Myosin light chain kinase, purified from chicken gizzard is assayed in the presence of 100 nM calmodulin, 100 μM CaCl2, 50 mM Hepes, 5 mM MgCI,, 1 mM dithiothreitol and 0.1 mg BSA/ml at pH 7.5 using a synthetic peptide based on the smooth-muscle myosin light-chain phosphorylation site and in the presence of 15 μM [γ-32P]ATP, in a final volume of 50 μL. Incorporation of radioactive phosphate is monitored on phosphocellulose filters as described above. ASK-γ, a plant homologue of GSK-3, is expressed as a glutathione-S-transferase fusion protein in Escherichia coli and purified on glutathione-agarose. ASK-γ kinase is assayed, for 10 minutes at 30 °C, with 5 μg myelin basic protein, in the presence of 15 μM [γ-32P]ATP in a final volume of 30 μL. The phosphorylated myelin basic protein is recovered on Whatman P81 phosphocellulose paper as described for the p34cdc2/cyclin B kinase. Insulin receptor tyrosine kinase domain (CIRK-41) is overexpressed in a baculovirus system and purified to homogeneity. Its kinase activity is assayed, for 10 minutes at 30 °C, with 5 μg Raytide, in the presence of 15 μM [γ-32P]ATP, in a final volume of 30 μL. The phosphorylated Raytide is recovered on Whatman P81 phosphocellulose paper as described for the p34cdc2/cyclin B kinase. c-src kinase is purified from infected Sf9 cells. The v-abl kinase is expressed in E. coli and affinity purified on IgG Affigel 10. Both kinases are assayed for 10 minutes at 30 °C, with 5 μg Raytide, in the presence of 15 μM [γ-32P]ATP, in a final volume of 30 μL. The phosphorylated Raytide is recovered on Whatman P81 phosphocellulose paper as described for the p34cdc2/cyclin B kinase.

Cell Assay: [1]

Cell lines Leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, breast cancer
Concentrations 0.01 - 100 μM
Incubation Time 48 hours
Method 60 human tumour cell lines comprising nine tumor types are cultured for 24 hours prior to a 48-hour continuous exposure to 0.01-100 μM roscovitine. A sulforhodaminine B protein assay is used to estimate the cytotoxicity.

Animal Study: [4]

Animal Models A4573 cells are injected s.c. into the right posterior flank of CD1 nu/nu mice.
Formulation Roscovitine is dissolved in either absolute methanol or DMSO and then diluted in 10% Tween 80, 20% N-N-dimethylacetamide, and 70% polyethylene glycol 400.
Dosages ≤50 mg/kg
Administration Administered via i.p.
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Meijer L, et al. Eur J Biochem, 1997, 243(1-2), 527-536.

[2] Pippin JW, et al. J Clin Invest, 1997, 100(10), 2512-2520.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-10-24)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02160730 Recruiting Cushings Disease Shlomo Melmed, MD|National Institutes of Health (NIH)|Ced  ...more Shlomo Melmed, MD|National Institutes of Health (NIH)|Cedars-Sinai Medical Center May 2014 Phase 2
NCT01333423 Withdrawn Breast Cancer M.D. Anderson Cancer Center|National Institutes of Health  ...more M.D. Anderson Cancer Center|National Institutes of Health (NIH) September 2012 Phase 1
NCT00999401 Recruiting Advanced Solid Tumors Cyclacel Pharmaceuticals, Inc. February 2009 Phase 1
NCT00372073 Terminated Non-small Cell Lung Cancer Cyclacel Pharmaceuticals, Inc. July 2006 Phase 2

Chemical Information

Download Roscovitine (Seliciclib,CYC202) SDF
Molecular Weight (MW) 354.45
Formula

C19H26N6O

CAS No. 186692-46-6
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 71 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol 6 mg/mL (16 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R)-2-(6-(benzylamino)-9-isopropyl-9H-purin-2-ylamino)butan-1-ol

Research Area

Customer Reviews (4)


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Rating
Source PNAS 2011 108, 8417. Roscovitine (Seliciclib,CYC202) purchased from Selleck
Method Western blotting, Wst-1 proliferation assay, radioimmunoassays
Cell Lines AtT20 cells
Concentrations 0-20 µM
Incubation Time 24/48 h
Results Treatment with R-roscovitine led to decreased cell number by 24 h (Fig. A). Western blot analysis of protein extracts derived from R-roscovitine-treated cells revealed evidence for cell cycle arrest, including decreased cyclin E, increased p27Kip1, p57Kip2, and p21Cip1 expression, as well as reduced Thr821 phosphorylation of Rb (Fig. B). R-roscovitine treatment also induced senescent features by 48 h as evidenced by increased β -gal expression (Fig. C). Consistent with decreased cell viability, we detected decreased ACTH concentrations in culture medium derived from R-roscovitine-treated AtT20 cells (Fig. D). Western blot analysis of protein extracts derived from R-roscovitine-treated AtT20 cells showed suppressed ACTH expression (Fig. E). These results indicate that R-roscovitine targets cdk2/cyclin E-mediated cell cycle progression, and also inhibits corticotroph ACTH protein expression.

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Rating
Source PNAS 2011 108, 8417. Roscovitine (Seliciclib,CYC202) purchased from Selleck
Method Western blotting, Fluorescent Microscopy, Confocal Imaging
Cell Lines Tumor xenografts
Concentrations 150 mg/kg
Incubation Time 15 d
Results R-roscovitine caused approximately 50% weight reduction of dissected tumor xenografts(Fig. A). Consistent with the in vitro observations, Western blot and immunohistochemistry analysis of tumor specimens showed suppressed ACTH and PCNA protein expression by R-roscovitine (Fig. B and C). R-roscovitine-treated mice exhibited more than 50% reduction in plasma ACTH levels ), and approximately 50% reduction in serum corticosterone levels.

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Rating
Source J Hematol Oncol 2012 7, 53. Roscovitine (Seliciclib,CYC202) purchased from Selleck
Method Western Blot/immunofluoresence
Cell Lines Isolated granular neurons
Concentrations 20 uM
Incubation Time 24 h
Results Application of roscovitine significantly suppressed T288 phosphorylation of Aurora-A associated with reduction of S251 phosphorylation of NDEL1, which was confirmed by Western blotting and immunocytochemistry.

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Rating
Source University of Hong Kong. Roscovitine (Seliciclib,CYC202) purchased from Selleck
Method Oil-Red-O/SA-β-gal staining
Cell Lines ApoE-/- mice
Concentrations
Incubation Time 18 weeks
Results Chronic treatment with roscovitine attenuates the development of atherosclerosis in ApoE-/- mice.

Product Citations (8)

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