AT7519 trifluoroacetate
(Synonyms: 4-[(2,6-二氯苯甲酰基)氨基]-N-4-哌啶基-1H-吡唑-3-甲酰胺三氟乙酸盐,AT 7519 trifluoroacetate;AT-7519 trifluoroacetate) 目录号 : GC15597
AT7519 (AT7519M) TFA 作为一种有效的 CDK 抑制剂,对 CDK1、CDK2、CDK4 到 CDK6 和 CDK9 的 IC50 分别为 210、47、100、13、170 和 <10 nM。
Cas No.:1431697-85-6
Sample solution is provided at 25 µL, 10mM.
AT7519 trifluoroacetate as a potent inhibitor of CDKs, with IC50s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.
AT7519 (0-4 μM) results in dose-dependent cytotoxicity with IC50s ranging from 0.5 to 2 μM in MM cells, and this induced cytotoxicity is associated with GSK-3β activation independent of transcriptional inhibition. AT7519 overcomes proliferative advantage conferred by cytokines and the protective effect of BMSC. AT7519 (0.5 μM) induces apoptosis of MM cells in a time-dependent manner. Moreover, AT7519 (0.5 μM) inhibits phosphorylation of RNA polymerase II CTD and partially inhibits RNA synthesis in MM.1S cells[1]. AT7519 (250 nM) inhibits cell cycle progression in human tumor cell lines. AT7519 also induces apoptosis of human tumor cell lines[2]. AT7519 (100-700 nM) induces apoptosis in leukemia cell lines. AT7519 also inhibits transcription in human tumor cell lines. Furthermore, AT7519 inhibits RNA polymerase II and reduces antiapoptotic protein levels[3].
AT7519 inhibits tumor growth in a human MM xenograft mouse model[1]. AT7519 (4.6 and 9.1 mg/kg/dose) inhibits the growth of early-stage HCT116 tumor xenografts. AT7519 (10 mg/kg, i.p.) also inhibits the target CDKs in HCT116 tumor-bearing BALB/c nude mice[2].
References:
[1]. Santo L, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36.
[2]. Squires MS, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.
[3]. Squires MS, et al. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8.
Cell experiment: | AT7519's effects on viability of MM cell lines, primary MM cells, and PBMNCs is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. DNA synthesis is measured by tritiated thymidine uptake (3H-TdR). MM cells (2-3 × 104 cells/well) are incubated in 96-well culture plates with media and different concentrations of AT7519 and/or recombinant IL-6 (10 ng/mL) or IGF-1 (50 ng/mL) for 24 or 48 h at 37°C and 3H-TdR incorporation is measured. |
Animal experiment: | To evaluate the in vivo anti-MM activity of AT7519, male SCID mice are inoculated subcutaneously with 5×106 MM.1S cells in 100 μL serum-free RPMI 1640 medium. When tumors are measurable, mice are treated intraperitoneally (IP) with vehicle or AT7519 dissolved in saline 0.9%. The first group of 10 mice is treated with 15 mg/kg once a day for five days for 2 weeks, and the second group is treated with 15 mg/kg once a day three times a week for four consecutive weeks. The control group receives the carrier alone at the same schedule. Tumor size is measured every alternate day in 2 dimensions using calipers, and tumor volume is calculated with the formula: V= 0.5 a × b2 (a= long diameter of the tumor, b= short diameter of the tumor). Animals are sacrificed when the tumor reaches 2 cm3 or when the tumor is ulcerated. Survival and tumor growth are evaluated from the first day of treatment until death. |
References: [1]. Santo L, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36. |
Cas No. | 1431697-85-6 | SDF | |
别名 | 4-[(2,6-二氯苯甲酰基)氨基]-N-4-哌啶基-1H-吡唑-3-甲酰胺三氟乙酸盐,AT 7519 trifluoroacetate;AT-7519 trifluoroacetate | ||
化学名 | 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide;2,2,2-trifluoroacetic acid | ||
Canonical SMILES | C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl.C(=O)(C(F)(F)F)O | ||
分子式 | C18H18Cl2F3N5O4 | 分子量 | 496.27 |
溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
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1 mg | 5 mg | 10 mg |
1 mM | 2.015 mL | 10.0752 mL | 20.1503 mL |
5 mM | 0.403 mL | 2.015 mL | 4.0301 mL |
10 mM | 0.2015 mL | 1.0075 mL | 2.015 mL |
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给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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- Purity: >98.00%
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