Mubritinib (TAK 165) (Synonyms: TAK-165) |
| Catalog No.GC10250 |
Mubritinib (TAK 165) is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 6nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 366017-09-6
Sample solution is provided at 25 µL, 10mM.
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Mubritinib (TAK 165) is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 6nM[1]. The erbB2 (also known as HER2 or neu) is a receptor tyrosine kinase with intrinsic tyrosine kinase activity[2]. When activated, HER2 provides the cell with potent proliferative and anti-apoptosis signals and it is the major driver of tumor development and progression[3]. Mubritinib is commonly used for research in cancers such as breast cancer, bladder cancer, and acute myeloid leukemia[4][5].
In vitro, BTSCs cells were treated with 500nM mubritinib for 24h, bioenergetic assays and rescue experiments showed that mubritinib targets complex I of the electron transport chain, thereby impairing BTSCs self-renewal and proliferation; flow cytometric quantitation showed a significant increase in the percentage of cells in the G1 phase and a decrease in the percentage of cells in the S phase in the mubritinib-treated BTSCs; gene expression profiling and Western blot analysis revealed that mubritinib disrupts the AMPK/p27Kip1 pathway, leading to cell cycle impairment[6].
In vivo, in the xenograft model, after the tumor volume reached 100–150mm3 , mice were intraperitoneal injected with 100μl of mubritinib (10mg/kg, once a day) and 100μl of cisplatin (5mg/kg, once a week) for 18 days，and the combination therapy of mubritinib and cisplatin significantly reduced the mean volume and weight of grafts and inhibited the expression of Ki-67, PI3K, mTOR, and 4EBP1 in tumor tissues[7].
References:
[1] Nagasawa, J., Mizokami, A., Koshida, K., Yoshida, S., Naito, K., & Namiki, M. (2006). Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo. International journal of urology : official journal of the Japanese Urological Association, 13(5), 587–592.
[2] Tan, M., & Yu, D. (2007). Molecular mechanisms of erbB2-mediated breast cancer chemoresistance. Advances in experimental medicine and biology, 608, 119–129.
[3] Moasser M. M. (2007). The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene, 26(45), 6469–6487.
[4] Gutierrez, C., & Schiff, R. (2011). HER2: biology, detection, and clinical implications. Archives of pathology & laboratory medicine, 135(1), 55–62.
[5] Baccelli, I., Gareau, Y., Lehnertz, B., Gingras, S., Spinella, J. F., Corneau, S., Mayotte, N., Girard, S., Frechette, M., Blouin-Chagnon, V., Leveillé, K., Boivin, I., MacRae, T., Krosl, J., Thiollier, C., Lavallée, V. P., Kanshin, E., Bertomeu, T., Coulombe-Huntington, J., St-Denis, C., … Sauvageau, G. (2019). Mubritinib Targets the Electron Transport Chain Complex I and Reveals the Landscape of OXPHOS Dependency in Acute Myeloid Leukemia. Cancer cell, 36(1), 84–99.e8.
[6] Burban, A., Tessier, C., Larroquette, M., Guyon, J., Lubiato, C., Pinglaut, M., Toujas, M., Galvis, J., Dartigues, B., Georget, E., Luchman, H. A., Weiss, S., Cappellen, D., Nicot, N., Klink, B., Nikolski, M., Brisson, L., Mathivet, T., Bikfalvi, A., Daubon, T., … Sharanek, A. (2025). Exploiting metabolic vulnerability in glioblastoma using a brain-penetrant drug with a safe profile. EMBO molecular medicine, 17(3), 469–503.
[7] Dong, J., Zhu, D., Chen, M., Wang, T., Gao, Y., & Liu, W. (2022). Mubritinib enhanced the inhibiting function of cisplatin in lung cancer by interfering with mitochondrial function. Thoracic cancer, 13(10), 1513–1524.
| Cell experiment [1]: | |
Cell lines | BTSCs cells |
Preparation Method | BTSCs were dissociated into single cell suspension using Accutase and 3 × 105 cells were plated in T25 flasks and treated with 500nM mubritinib (TAK 165) . After 24h, the cells were dissociated into single-cell suspensions, harvested and fixed with 70% ethanol overnight at 4°C. The cells were washed with 1X PBS and stained with FxCycle PI/RNase staining solution (Molecular Probes, #F10797) (Sharanek et al, 2021). The fluorescence was analysed by flow cytometry (Accuri C6 flow cytometer). The fractions of G0/G1-, S- and G2-phase cells were determined using the Watson pragmatic algorithm of FlowJo software. For gene expression profiling and Western blot analysis, cells were harvested for further investigation. |
Reaction Conditions | 500nM; 24h |
Applications | Mubritinib (TAK 165) impaired BTSCs self-renewal and proliferation, increased the percentage of cells in the G1 phase and decreased the percentage of cells in the S phase. Gene expression profiling and Western blot analysis revealed that mubritinib (TAK 165) disrupts the AMPK/p27Kip1 pathway, leading to cell cycle impairment. |
| Animal experiment [2]: | |
Animal models | male BALB/c-Nu mice |
Preparation Method | NCI-H1975 cells 2 ×106 were subcutaneously injected into the right flank of each mouse, and the growth of the transplanted tumor was continuously monitored. When the tumor volume reached 100–150mm3 , the mice were divided into four groups with five mice in each group: (1) control (Ctr): intraperitoneal injection of 100μl of PBS once a day; (2) cisplatin (Pt): intraperitoneal injection of 100 μl of cisplatin (5 mg/kg), once a week; (3) mubritinib (Mu): intraperitoneal injection of 100μl of mubritinib (10mg/kg), once a day for 18 consecutive days; and (4) combination (Com): combined injection of cisplatin and mubritinib as the monotherapy group. During treatment, the long and short diameters of the transplanted tumor were measured, and the volumes were calculated. At the end of the treatment, mice were sacrificed by inhalation of an overdose of ether. The tumor, heart, liver, spleen, lung, and kidney were dissected and fixed with formalin. |
Dosage form | 10mg/kg/day for 18 days; i.p. |
Applications | Combination therapy of mubritinib and cisplatin significantly reduced the mean volume and weight of grafts and inhibited the expression of Ki-67, PI3K, mTOR, and 4EBP1 in tumor tissues. |
References: | |
| Cas No. | 366017-09-6 | SDF | |
| Synonyms | TAK-165 | ||
| Chemical Name | 4-[[4-[4-(triazol-1-yl)butyl]phenoxy]methyl]-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole | ||
| Canonical SMILES | C1=CC(=CC=C1CCCCN2C=CN=N2)OCC3=COC(=N3)C=CC4=CC=C(C=C4)C(F)(F)F | ||
| Formula | C25H23F3N4O2 | M.Wt | 468.47 |
| Solubility | ≥ 76.9mg/mL in DMSO with gentle warming | 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 | 2.1346 mL | 10.673 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 |
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- Purity: >99.50%
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