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Mubritinib (TAK 165) HER2 inhibitor

Name: Mubritinib (TAK 165)
Brand: Selleck Chemicals
SKU: S2216
Availability: InStock
Rating: 5 (39 reviews)

Catalog No.S2216 Purity:99.94%

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.

Chemical Structure

Molecular Weight: 468.47

Purity & Quality Control

Batch: Purity: 99.94%

99.94

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Signaling Pathway

HER2 Signaling Pathway

Mechanism of Action

Targets

HER2/ErbB2 ^[1]
(BT-474 cells)

6.0 nM

In vitro
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]
Kinase Assay	Inhibition of HER2/erbB2 tyrosine kinase activity
Kinase Assay	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 Research	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	pERK / ERK / pAKT / AKT / p-STAT3 / STAT3 / pHER2 / HER2 c-myc / p21 / p27		25407459
	Growth inhibition assay	Cell viability		25407459

In Vivo
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]
Animal Research	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

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00034281	Completed	Breast Neoplasm\|Pancreatic Neoplasm\|Lung Neoplasm\|Ovarian Neoplasm\|Renal Neoplasm	Takeda	June 2002	Phase 1

References

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

Chemical Information

Molecular Weight	468.47	Formula	C₂₅H₂₃F₃N₄O₂
CAS No.	366017-09-6	SDF	Download SDF
Synonyms	N/A
Smiles	C1=CC(=CC=C1CCCCN2C=CN=N2)OCC3=COC(=N3)C=CC4=CC=C(C=C4)C(F)(F)F

Storage and Stability

Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
			1 month-20°Cin solvent

In vitro
Batch:

DMSO : 13 mg/mL ( (27.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
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.
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.
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.

Preparing Stock Solutions

Molarity Calculator

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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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