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186692-46-6 分子结构
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(2R)-2-{[6-(benzylamino)-9-(propan-2-yl)-9H-purin-2-yl]amino}butan-1-ol

ChemBase编号:72547
分子式:C19H26N6O
平均质量:354.44934
单一同位素质量:354.21680948
SMILES和InChIs

SMILES:
n1c2c(c(nc1N[C@@H](CO)CC)NCc1ccccc1)ncn2C(C)C
Canonical SMILES:
CC[C@@H](Nc1nc(NCc2ccccc2)c2c(n1)n(cn2)C(C)C)CO
InChI:
InChI=1S/C19H26N6O/c1-4-15(11-26)22-19-23-17(20-10-14-8-6-5-7-9-14)16-18(24-19)25(12-21-16)13(2)3/h5-9,12-13,15,26H,4,10-11H2,1-3H3,(H2,20,22,23,24)/t15-/m1/s1
InChIKey:
BTIHMVBBUGXLCJ-OAHLLOKOSA-N

引用这个纪录

CBID:72547 http://www.chembase.cn/molecule-72547.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(2R)-2-{[6-(benzylamino)-9-(propan-2-yl)-9H-purin-2-yl]amino}butan-1-ol
IUPAC传统名
seliciclib
别名
Roscovitine
Seliciclib
CYC202
Seliciclib
R-roscovitine
Roscovitine(CYC202)
2-(R)-[[9-(1-Methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-1-butanol
6-(Benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine
Roscovitine
(2R)-2-[[9-(1-methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-1-butanol
(R)-2-[[9-(1-methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-1-butanol
2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine
CYC 202
(R)-Roscovitine
Roscovitin
Roscovitine
CAS号
186692-46-6
MDL号
MFCD02266401
PubChem SID
162037472
24278682
PubChem CID
160355
CHEMBL
14762
医学主题词(MeSH)
roscovitine
维基百科标题
Seliciclib

数据来源

数据来源

所有数据来源 商品来源 非商品来源

理论计算性质

理论计算性质

JChem
Acid pKa 14.336885  质子受体
质子供体 LogD (pH = 5.5) 2.8926105 
LogD (pH = 7.4) 2.8927808  Log P 2.8927832 
摩尔折射率 106.1443 cm3 极化性 39.333714 Å3
极化表面积 87.89 Å2 可自由旋转的化学键
里宾斯基五规则 true 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
保存条件
-20°C expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
个人保护装置
Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter expand 查看数据来源
保存温度
-20°C expand 查看数据来源
作用靶点
CDK expand 查看数据来源
相关基因信息
human ... CDK1(983), CDKN1A(1026), CDKN1B(1027), CDKN1C(1028), CDKN2A(1029), CDKN2B(1030), CDKN2C(1031), CDKN2D(1032), CDKN3(1033)mouse ... CDK1(12534)rat ... CDK1(54237) expand 查看数据来源
纯度
≥98% (TLC) expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Wikipedia Wikipedia Sigma Aldrich Sigma Aldrich TRC TRC
Selleck Chemicals -  S1153 external link
Research Area
Description Cancer
Biological Activity
Description Roscovitine (Seliciclib, CYC202, R-roscovitine) is a potent and selective CDK inhibitor for Cdc2/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p53 with IC50 of 0.65 μM, 0.7 μM, 0.7 μM and 0.16 μM, respectively.
Targets Cdc2/cyclin B CDK2/cyclin A CDK2/cyclin E CDK5/p35
IC50 0.65 μM 0.7 μM 0.7 μM 0.16 μM [1]
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]
Clinical Trials Roscovitine is currently in Phase I clinical trial in patients with advanced solid tumors.
Features
Protocol
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
Methods 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.
Doses ≤50 mg/kg
Administration Administered via i.p.
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.
[3] Huber RJ, et al. J Cell Biochem, 2012, 113(3), 868-876.
[4] Tirado OM, et al. Cancer Res, 2005, 65(20), 9320-9327.
[5] Appleyard MV, et al. Int J Cancer, 2009, 124(2), 465-472.
Sigma Aldrich -  R7772 external link
Biochem/physiol Actions
Roscovitine is a potent, selective inhibitor of cyclin-dependent kinases.
Legal Information
Sold under license from CNRS
Toronto Research Chemicals -  R684000 external link
Roscovitine is a potent and selective inhibitor of cyclin-dependent kinases (CDKs). Roscovitine has been found to produce apoptosis in treated cancerous cells of non-small cell lung cancer (NSCLC) and other cancers. Studies show that Roscovitine displays

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