TAK-901
(Synonyms: 5-[3-(乙基磺酰基)苯基]-3,8-二甲基-N-(1-甲基-4-哌啶基)-9H-吡啶并[2,3-B]吲哚-7-甲酰胺) 目录号 : GC11085
A non-selective inhibitor of Aurora kinases
Cas No.:934541-31-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | Enzyme activities of Aurora A/TPX2 and Aurora B/INCENP complexes are assayed at room temperature in buffer containing serially diluted TAK-901, and the product is quantified using IMAP detection reagents. Aurora A/TPX2 (2 nM) is assayed with 100 nM FL-Kemptide and 1 mM ATP. Aurora B/INCENP (0.8 nM) is assayed with 100 nM 5-carboxy-fluorescein-GRTGRRNSI-NH2 (FL-PKAtide) and 10 mM ATP. For time-dependent inhibition, Aurora B/INCENP is incubated with TAK-901 for 1 hour at room temperature followed by addition of 150 mM ATP to initiate the reaction[1]. |
Cell experiment: | Cells are plated in 96-well microtiter plates and incubated with serial dilutions of TAK-901 for 72 hours. Cell proliferation is determined by ELISA analysis of bromodeoxyuridine (BrdUrd) incorporation into DNA. IMR-90 immortalized lung fibroblasts are seeded in 96-well microtiter plates and cultured for 3 to 4 days until confluent. Cells are then incubated with serial dilutions of TAK-901 for 72 hours. The MTS assay is conducted[1]. |
Animal experiment: | Mice: Tumor-bearing mice or rats are treated intravenously twice daily (b.i.d.) with either vehicle or TAK-901 on 2 consecutive days per week or every other day for 2 or 3 cycles. The antitumor activity of TAK-901 in human tumor and leukemia xenograft models are monitored[1]. Nude rats bearing A2780 tumors averaging 250 to 500 mg receive an intravenous dose of TAK-901. Plasma samples are collected by terminal cardiac puncture under CO2 anesthesia. Tumors are dissected and snap-frozen at -80°C[1]. |
References: [1]. Farrell P, et al. Biological characterization of TAK-901, an investigational, novel, multitargeted Aurora B kinase inhibitor. Mol Cancer Ther. 2013 Apr;12(4):460-70. | |
IC50: 0.0017, 0.021 for Aurora-B/INCENP and Aurora-A/TPX2, respectively
Protein kinases Aurora A, B, and C play crucial roles during mitosis and cell division, are frequently elevated in cancer, and represent attractive targets for therapeutic intervention. TAK-901 is a novel, multitargeted Aurora B kinase inhibitor derived from a novel azacarboline kinase hinge-binder chemotype.
In vitro: TAK-901 exhibited time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. Consistently, TAK-901 suppressed cellular histone H3 phosphorylation and induced polyploidy. In various human cancer cell lines, TAK-901 inhibited cell proliferation with effective concentration values from 40 to 500 nmol/L. TAK-901 potently inhibited only a few kinases other than Aurora B in intact cells, including FLT3 and FGFR2 [1].
In vivo: In rodent xenografts, TAK-901 exhibited potent activity against multiple human solid tumor types, and complete regression was found in the ovarian cancer A2780 model. In vivo biomarker studies showed that TAK-901 induced PD responses consistent with Aurora B inhibition and correlating with retention of TAK-901 in tumor tissue. [2].
Clinical trials: An open-label, dose escalation, phase I study has been conducted to identify the MTD and PK profile of TAK-901 in adult patients with advanced solid tumors or lymphoma.
Reference:
[1] Farrell P, Shi L, Matuszkiewicz J, Balakrishna D, Hoshino T, Zhang L, Elliott S, Fabrey R, Lee B, Halkowycz P, Sang B, Ishino S, Nomura T, Teratani M, Ohta Y, Grimshaw C, Paraselli B, Satou T, de Jong R. Biological characterization of TAK-901, an investigational, novel, multitargeted Aurora B kinase inhibitor. Mol Cancer Ther. 2013;12(4):460-70.
| Cas No. | 934541-31-8 | SDF | |
| 别名 | 5-[3-(乙基磺酰基)苯基]-3,8-二甲基-N-(1-甲基-4-哌啶基)-9H-吡啶并[2,3-B]吲哚-7-甲酰胺 | ||
| 化学名 | 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide | ||
| Canonical SMILES | CCS(=O)(=O)C1=CC=CC(=C1)C2=CC(=C(C3=C2C4=CC(=CN=C4N3)C)C)C(=O)NC5CCN(CC5)C | ||
| 分子式 | C28H32N4O3S | 分子量 | 504.64 |
| 溶解度 | ≥ 25.25 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9816 mL | 9.9081 mL | 19.8161 mL |
| 5 mM | 0.3963 mL | 1.9816 mL | 3.9632 mL |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9816 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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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