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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Mubritinib (formerly also known as TAK165; TAK-165) is a novel, potent, selective and investigational inhibitor of HER2/ErbB2 with potential anticancer activity. It has no effect on EGFR, FGFR, PDGFR, JAK1, Src, or Blk in BT-474 cells, but it inhibits HER2/ErbB2 with an IC50 of 6 nM in these cells. Takeda developed it and it has successfully completed phase I clinical trials for the treatment of cancer (though it may have been discontinued since December 2008). Mubritinib exhibits significant in vivo antitumor efficacy against bladder, breast, and prostate cancer xenografts in vivo, as well as strong anti-proliferative activity against ErbB2-overexpressing cancer cell lines, with an IC50 of 5 nM in BT474 breast cancer cells.
| Targets |
HER2 (IC50 = 6 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
On 24-well plates, BT-474 cells are plated and allowed to grow overnight. Then, different doses of mubritinib are added. The cells are harvested directly into 200 μL of sodium dodecyl sulfate (SDS)-sample buffer after two hours of incubation. On a 7.5% to 15% gradient SDS–polyacrylamide gel electrophoresis (PAGE), aliquots with equal volumes of total cell extract are run. After the electrophoresis process, proteins are blotted onto a PVDF membrane using a primary antibody specific to the desired western blot analysis. A technique known as enhanced chemiluminescent (ECL) detection is used to detect proteins. The LAS-1000 plus lumino-image analyzer measures the degree of tyrosine phosphorylation of HER2/erbB2. Mubritinib's 50% inhibitory concentration (IC50) on HER2/erbB2 phosphorylation is determined by analyzing a dose-response curve produced by least-squares linear regression of the response with SAS software.
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| Cell Assay |
Cells are seeded into 6-well plates and cultured overnight. Mubritinib is then added at various concentrations, and the cells are treated continuously for 72 hours. After the incubation period, cells are counted for the measurement of antiproliferative activity.
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| Animal Protocol |
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| References | ||
| Additional Infomation |
Mubritinib has been used in trials studying the treatment of Lung Neoplasm, Renal Neoplasm, Breast Neoplasm, Ovarian Neoplasm, and Pancreatic Neoplasm.
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| Molecular Formula |
C25H23F3N4O2
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|---|---|---|
| Molecular Weight |
468.47
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| Exact Mass |
468.177
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| Elemental Analysis |
C, 64.10; H, 4.95; F, 12.17; N, 11.96; O, 6.83
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| CAS # |
366017-09-6
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| Related CAS # |
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| PubChem CID |
6444692
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| Appearance |
white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
620.9±65.0 °C at 760 mmHg
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| Melting Point |
158.0 to 162.0 °C
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| Flash Point |
329.3±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.578
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| LogP |
5.91
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
34
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C([H])=C([H])C(=C([H])C=1[H])/C(/[H])=C(\[H])/C1=NC(=C([H])O1)C([H])([H])OC1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C([H])=C([H])N=N1)(F)F
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| InChi Key |
ZTFBIUXIQYRUNT-MDWZMJQESA-N
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| InChi Code |
InChI=1S/C25H23F3N4O2/c26-25(27,28)21-9-4-20(5-10-21)8-13-24-30-22(18-34-24)17-33-23-11-6-19(7-12-23)3-1-2-15-32-16-14-29-31-32/h4-14,16,18H,1-3,15,17H2/b13-8+
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| Chemical Name |
4-[[4-[4-(triazol-1-yl)butyl]phenoxy]methyl]-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole
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| Synonyms |
TAK-165; Mubritinib; TAK 165; TAK165
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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) |
Solubility in Formulation 1: 2.5 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 1% DMSO+30% polyethylene glycol+1% Tween 80: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1346 mL | 10.6730 mL | 21.3461 mL | |
| 5 mM | 0.4269 mL | 2.1346 mL | 4.2692 mL | |
| 10 mM | 0.2135 mL | 1.0673 mL | 2.1346 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 |
| NCT00034281 | Completed | Drug: TAK-165 | Breast Neoplasm Lung Neoplasm |
Takeda | June 2002 | Phase 1 |
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