Mubritinib (TAK 165)

Catalog No.S2216 Batch:S221602

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Technical Data

Formula

C25H23F3N4O2
Molecular Weight 468.47 CAS No. 366017-09-6
Solubility (25°C)* In vitro DMSO 93 mg/mL (198.51 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description A potent inhibitor of HER2/ErbB2 with IC50 of 6 nM in BT-474 cell, Mubritinib (TAK-165) shows no activity to EGFR, FGFR, PDGFR, JAK1, Src and Blk in the same cell line.
Targets
HER2/ErbB2 [1]
(BT-474 cells)
6.0 nM
In vitro

Mubritinib (TAK 165) displays > 4000-fold selectivity over other tyrosine kinases, such as EGFR, FGFR, PDGFR, Jak1, Src and Blk. It even at low concentration of 0.1 μM significantly blocks HER2 phosphorylation, leading to the downregulation of PI3K-Akt and MAPK pathway in cell line BT474 with high level of HER2. This compound not only exhibits highly potent antiproliferative effect in ErbB2-overexpressing cancer cell line BT474 with an IC50 of 5 nM, but also displays marked antiproliferative effects in cell lines with HER2 expressed weakly with IC50 of 53 nM, 90 nM and 91 nM for LNCaP, LN-REC4 and T24, respectively. It displays no inhibitory activities against PC-3 cells with HER2 expressed very faintly with IC50 of 4.62 μM, as well as EGFR-overexpressing HT1376 and ACHN cell lines with IC50 of >25 μM. [1]
In vivo

Mubritinib (TAK 165) significantly inhibits LN-REC4 xenograft with treatment/control tumor volume ratio of 26.5%. Although ineffective to inhibit the growth of UMUC-3 and ACHN cells in vitro (IC50s of 1.812 and >25 μM, respectively), oral administration of this compound (10 or 20 mg/kg per day) significantly inhibits the growth of UMUC-3 and ACHN xenografts with treatment/control tumor volume ratio of 22.9% and 26%, respectively, as compared with 20 mg/kg which is ineffective to UMUC-3 tumor growth. [1]

Protocol (from reference)

Kinase Assay:

[1]
  • Inhibition of HER2/erbB2 tyrosine kinase activity

    BT-474 cells are seeded on 24-well plates and cultured overnight. Mubritinib (TAK 165) is then added at various concentrations. After incubation for 2 hours, the cells are harvested directly into sodium dodecyl sulfate (SDS)-sample buffer (200 μL). Aliquots containing equal amounts of total cell extract are run on 7.5% to 15% gradient SDS–polyacrylamide gel electrophoresis (PAGE). Following electrophoresis, proteins are transferred onto a polyvinylidene fluoride (PVDF) membrane, for western blot analysis using a relevant primary antibody. Detection of protein is accomplished by an enhanced chemiluminescent (ECL) detection method. The extent of tyrosine phosphorylation of HER2/erbB2 is measured by the LAS-1000 plus lumino-image analyser. The concentration of this compound that inhibits HER2/erbB2 phosphorylation by 50% (IC50) is calculated from a dose–response curve generated by least-squares linear regression of the response using SAS software.
Cell Assay:

[1]
  • Cell lines

    BT474, HT1376, UMUC-3, T24, ACHN, DU-145, PC-3, LN-REC4, and LNCaP cells

  • Concentrations

    Dissolved in DMSO, final concentrations ~50 mM

  • Incubation Time

    72 hours

  • Method

    Mubritinib (TAK 165) is added at various concentrations after cells are seeded into 6-well plates and cultured overnight. The cells are treated continuously for 72 hours with this compound. After the incubation period, cells are counted for the measurement of antiproliferative activity.
Animal Study:

[1]
  • Animal Models

    Athymic nude mice (BALB/c nu/nμ) and SCID mice (C.B.-17 Scid/Scid) are implanted subcutaneously with UMUC-3, LN-REC4 or ACHN cells

  • Dosages

    10 or 20 mg/kg/day

  • Administration

    Orally twice daily

References

  • https://pubmed.ncbi.nlm.nih.gov/16771730/

Customer Product Validation

<p>(A) Cell proliferationanalysis of NB4 cells 24 h post-Mubritinib treatments(0–1 uM) as measured by MTT proliferation assay. (B) Representative images of cell cycle progression analysis of NB4 cells 24 h post 0.25 uM and 0.5 uM Mubritinib Treatment measured by BrdU flow cytometry.</p>

Data from [ Leuk Res , 2014 , 38(3), 402-10 ]

(d,e) HL60 and NB4 cell flow cytometric cycle proportion assay. The cells were treated with the indicated concentrations of TAK165 for 3 days. (f) A western blot analysis of c-myc, p21 and p27 protein in HL60 and NB4 cells. The cells were treated with the indicated concentrations of TAK165 for 3 days.

Data from [ , , Sci Rep, 2016, 6:24589 ]

The cells were treated with either brusatol (40 nM) or mubritinib (8 nM) alone and in combination for 2 h followed by treatment with increasing concentrations of oxaliplatin for 72 h. The differential impacts of Nrf2 and Her2 inhibition (A and B) in the survival rate of SW480/Res cells have been shown.

Data from [ , , Biomed Pharmacother, 2018, 103:755-766 ]

Selleck's Mubritinib (TAK 165) Has Been Cited by 40 Publications

Loss of ERα involved-HER2 induction mediated by the FOXO3a signaling pathway in fulvestrant-resistant breast cancer [ Biochem Biophys Res Commun, 2025, 742:151056] PubMed: 39626368
SF3B1 mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia [ Sci Adv, 2024, 10(12):eadl4018] PubMed: 38517966
A drug discovery pipeline for MAPK/ERK pathway inhibitors in C. elegans [ Cancer Res Commun, 2024, 10.1158/2767-9764.CRC-24-0221] PubMed: 39212544
Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2 [ Biochem Biophys Rep, 2023, 34:101436] PubMed: 36824069
Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2 [ Biochem Biophys Rep, 2023, 34:101436] PubMed: 36824069
The proteogenomic subtypes of acute myeloid leukemia [ Cancer Cell, 2022, 40(3):301-317.e12] PubMed: 35245447
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y] PubMed: 35118583
Hypoxia Regulates Endogenous Double-Stranded RNA ProductionviaReduced Mitochondrial DNA Transcription [ Front. Oncol, 2021-, Volume 11-] PubMed: None
Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional [ Nat Commun, 2021, 12(1):4566] PubMed: 34315881

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SHIPPING AND STORAGE
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