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Purity: ≥98%
TAK-901 (TAK901) is a novel and potent inhibitor of Aurora A/B kinases with potential antitumor activity. It inhibits Aurora A/B with IC50s of 21 nM and 15 nM, respectively, and shows little/no activity against JAK2, c-Src or Abl. TAK-901 displayed potent in vitro antiproliferative activity and high in vivo antitumor efficacy by binding to and inhibiting the activity of Aurora B, leading to a decrease in the proliferation of tumor cells that overexpress Aurora B.
| ln Vitro |
TAK-901 lowers cellular histone H3 phosphorylation and causes polyploidy in accordance with Aurora B suppression. It also shows time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. TAK-901, with effective concentration values ranging from 40 to 500 nM, suppresses cell proliferation in a variety of human cancer cell lines. Many kinases are inhibited when a large panel of kinases is examined in biochemical experiments. TAK-901, however, only weakly inhibits a few kinases in intact cells, such as FLT3 and FGFR2, aside from Aurora B [1].
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| ln Vivo |
TAK-901 shows strong action against many human solid tumor types in mouse xenografts, and it completely resolves the A2780 form of ovarian cancer. Additionally, TAK-901 showed strong efficacy against a number of leukemia models. TAK-901 produces pharmacologic effects that are correlated with its retention in tumor tissue and consistent with suppression of Aurora B[1].
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| Additional Infomation |
TAK-901 has been used in trials studying the treatment of Lymphoma, Myelofibrosis, Multiple Myeloma, Myeloid Metaplasia, and Advanced Solid Tumors, among others.
Aurora B Serine/Threonine Kinase Inhibitor TAK-901 is a small-molecule inhibitor of the serine-threonine kinase Aurora B with potential antineoplastic activity. Aurora B kinase inhibitor TAK-901 binds to and inhibits the activity of Aurora B, which may result in a decrease in the proliferation of tumor cells that overexpress Aurora B. Aurora B is a positive regulator of mitosis that functions in the attachment of the mitotic spindle to the centromere; the segregation of sister chromatids to each daughter cell; and the separation of daughter cells during cytokinesis. This serine/threonine kinase may be amplified and overexpressed by a variety of cancer cell types. |
| Molecular Formula |
C28H32N4O3S
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| Molecular Weight |
504.64
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| Exact Mass |
504.219
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| CAS # |
934541-31-8
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| Related CAS # |
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| PubChem CID |
16124208
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
761.7±60.0 °C at 760 mmHg
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| Flash Point |
414.5±32.9 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.685
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| LogP |
3.65
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
884
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WKDACQVEJIVHMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H32N4O3S/c1-5-36(34,35)21-8-6-7-19(14-21)23-15-22(28(33)30-20-9-11-32(4)12-10-20)18(3)26-25(23)24-13-17(2)16-29-27(24)31-26/h6-8,13-16,20H,5,9-12H2,1-4H3,(H,29,31)(H,30,33)
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| Chemical Name |
5-(3-(ethylsulfonyl)phenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00807677 | Completed | Drug: TAK-901 | Acute Myeloid Leukemia Acute Lymphoblastic Leukemia |
Millennium Pharmaceuticals, Inc. | March 2009 | Phase 1 |
| NCT00935844 | Completed | Drug: TAK-901 | Advanced Solid Tumors Lymphoma |
Millennium Pharmaceuticals, Inc. | October 2009 | Phase 1 |
A, chemical structure of TAK-901. B, TAK-901 inhibition of Aurora A and B kinase/coactivator complexes and kinetic data of the Aurora B/INCENP enzyme complex. C, kinase inhibition profile of TAK-901. D, enzyme reaction progression curves showing TAK-901 time-dependent binding to (D) and dissociation (E) from Aurora B/INCENP enzyme complex.Mol Cancer Ther. 2013 Apr;12(4):460-70. |
TAK-901 inactivates cellular Aurora B kinase and inhibits cell proliferation. A, immunoblot analysis of histone H3 phosphorylation in PC3 cells treated with TAK-901. B, PC3 cells were incubated for 48 hours with dimethyl sulfoxide or 0.2 μmol/L TAK-901 and stained for actin (green) and DNA (blue). C, DNA content histograms of HL60 cells after incubation for 48 hours with a concentration dilution series of TAK-901. D, TAK-901 EC50values for cell proliferation (DNA synthesis) inhibition in cells.Mol Cancer Ther. 2013 Apr;12(4):460-70. |
Profile of various TAK-901 kinase targets. A, MV4-11 cells, 2 μmol/L FLT3/MTK inhibitor. B, KATO-III cells, 10 μmol/L Aurora B inhibitor. C, profile of TAK-901 cellular activity against Aurora B kinase and several cross-reacting kinases. EC50values derived from dose–response immunoblotting or cellular reporter.Mol Cancer Ther. 2013 Apr;12(4):460-70. |
In vivoantitumor activity of TAK-901 in human tumor and leukemia xenograft models.Mol Cancer Ther. 2013 Apr;12(4):460-70. |
In vivoeffects of TAK-901 on Aurora B pharmacodynamic markers. A, histone H3 phosphorylation in nude rat A2780 xenograft tumors.B, polyploidy in nude mice A2780 xenograft tumors.Mol Cancer Ther. 2013 Apr;12(4):460-70. |
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