TAK-901 |
| Catalog No.GC11085 |
A non-selective inhibitor of Aurora kinases
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 934541-31-8
Sample solution is provided at 25 µL, 10mM.
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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.
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. | |
| Cas No. | 934541-31-8 | SDF | |
| Chemical Name | 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 | ||
| Formula | C28H32N4O3S | M.Wt | 504.64 |
| Solubility | ≥ 25.25 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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