5-N-(6-aminohexyl)-7-N-benzyl-3-(propan-2-yl)pyrazolo[1,5-a]pyrimidine-5,7-diamine hydrochloride

• ChemBase编号: 72751
• 分子式: C22H33ClN6
• 平均质量: 416.99062
• 单一同位素质量: 416.24552277
• SMILES: c1(cc(nc2n1ncc2C(C)C)NCCCCCCN)NCc1ccccc1.Cl
• Canonical SMILES: NCCCCCCNc1cc(NCc2ccccc2)n2c(n1)c(cn2)C(C)C.Cl
• InChI: InChI=1S/C22H32N6.ClH/c1-17(2)19-16-26-28-21(25-15-18-10-6-5-7-11-18)14-20(27-22(19)28)24-13-9-4-3-8-12-23;/h5-7,10-11,14,16-17,25H,3-4,8-9,12-13,15,23H2,1-2H3,(H,24,27);1H
• InChIKey: NVIJWMOQODWNFN-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 5-N-(6-aminohexyl)-7-N-benzyl-3-(propan-2-yl)pyrazolo[1,5-a]pyrimidine-5,7-diamine hydrochloride
• IUPAC传统名: 5-N-(6-aminohexyl)-7-N-benzyl-3-isopropylpyrazolo[1,5-a]pyrimidine-5,7-diamine hydrochloride
• 别名: BS-181 hydrochloride

登记号

• CAS号: 1092443-52-1
• PubChem SID: 162037672
• PubChem CID: 49867928

理论计算性质

• 极化表面积: 80.27 Å^2
• 可自由旋转的化学键: 11
• 里宾斯基五规则: true
• Acid pKa: 19.458256
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 0.08851656
• LogD (pH = 7.4): 1.2835636
• Log P: 3.9212356
• 摩尔折射率: 129.1932 cm^3
• 极化性: 44.122795 Å^3

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: CDK

产品相关信息

• 成盐信息: Hydrochloride

详细说明

Selleck Chemicals - S1572

Research Area

• Description: Cancer

Biological Activity

• Description: BS-181 is a highly selective CDK inhibitor for CDK7 with IC50 of 21 nM.
• Targets: CDK7
• IC50: 21 nM ^[1]
• In Vitro: BS-181 is a small molecule inhibitor of CDK7 in a cell-free environment, which displays more potential activity than roscovitine with IC 50 of 510 nM. Among the CDKs and other 69 kinases from many different classes, BS-181 shows high inhibitory selectivity for CDK7, inhibits CDK2 at concentrations lower than 1 μM which being inhibited 35-fold less potently (IC50 with 880 nM) than CDK7, shows slight inhibition for CDK1, CDK4, CDK5, CDK6 and CDK9 with IC50 values higher than 3.0 μM, and only shows inhibition for several kinases from other classes at high concentrations (>10 μM). BS-181 promotes cell cycle arrest and inhibits the cancer cell growth of a range of tumor types, including breast, lung, prostate and colorectal cancer with IC50 in the range of 11.5-37 μM. In MCF-7 cells, BS-181 inhibits the phosphorylation of the CDK7 substrate RNA polymerase II COOH-terminal domain (CTD), and promotes cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines. ^[1]
• In Vivo: BS-181 is stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. BS-181 inhibits the growth of MCF-7 xenografts in the nude mice model in a dose-dependent manner, with 25% and 50% reduction in tumor growth after 2 weeks of treatment at 10 mg/kg/day and 20 mg/kg/day, respectively without apparent toxicity. ^[1]
• Features: BS-181 shows higher inhibitory selectivity for CDK7 than other CDKs and kinases from many different classes.

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro kinase inhibition.: Inhibition of CDK7 activity is measured by incubation of increasing amounts of BS-181 with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50.
• Protocol: Cell Assay ^[1]
• Cell Lines: MCF-7 cells
• Concentrations: Dissolved in DMSO, final concentration ~50 μM
• Incubation Time: 24 hours
• Methods: MCF-7 cells are exposed to BS-181 for 24 hours. For the determination of cell cycle and apoptosis, cells are stained with propidium iodide or labeled with Annexin V-FITC, then labeled cells are acquired within 1 hour, by using the RXP cytomics software on a Beckman Coulter Elite ESP, and the data are analyzed using Flow Jo v7.2.5. For the assessment of CDKs, cells are lysed and analyzed by western blotting.
• Protocol: Animal Study ^[1]
• Animal Models: MCF-7 cells are established in female nu/nu-BALB/c athymic nude mice
• Formulation: Prepared in the vehicle of 10% DMSO / 50 mM HCl / 5% Tween 20 / 85% saline.
• Doses: 10 or 20 mg/kg
• Administration: Twice daily by i.p. injection

References

• References: [1] Ali S, et al. Cancer Res, 2009, 69(15), 6208-6215.

参考文献

• Ali S, et al. Cancer Res, 2009, 69(15), 6208-6215.