Mubritinib (TAK 165)

製品コードS2216 バッチS221601

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₅H₂₃F₃N₄O₂
	分子量	468.47	CAS No.	366017-09-6
Solubility (25°C)*	体外	DMSO	25 mg/mL (53.36 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Mubritinib (TAK-165) is a potent inhibitor of HER2/ErbB2 with IC50 of 6 nM in BT-474 cell; no activity to EGFR, FGFR, PDGFR, JAK1, Src and Blk in BT-474 cell line.
in vitro	Mubritinib displays > 4000-fold selectivity over other tyrosine kinases, such as EGFR, FGFR, PDGFR, Jak1, Src and Blk. Mubritinib 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. Mubritinib 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. Mubritinib 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 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 Mubritinib (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 Herceptin (20 mg/kg) which is ineffective to UMUC-3 tumor growth. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Inhibition of HER2/erbB2 tyrosine kinase activity
キナーゼアッセイ	BT-474 cells are seeded on 24-well plates and cultured overnight. Mubritinib 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 Mubritinib 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.
細胞アッセイ	細胞株	BT474, HT1376, UMUC-3, T24, ACHN, DU-145, PC-3, LN-REC4, and LNCaP cells
	濃度	Dissolved in DMSO, final concentrations ~50 mM
	反応時間	72 hours
	実験の流れ	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.
動物実験	動物モデル	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
	投薬量	10 or 20 mg/kg/day
	投与方法	Orally twice daily

参考

[1] Nagasawa J, et al. Int J Urol, 2006, 13(5), 587-592.

カスタマーフィードバック

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

: Data from [Data independently produced by , , Sci Rep, 2016, 6:24589]

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function [ Curr Biol, 2021, S0960-9822(21)00680-1]	PubMed: 34107301
HER2 mediates clinical resistance to the KRASG12C inhibitor sotorasib, which is overcome by co-targeting SHP2 [ Eur J Cancer, 2021, 159:16-23]	PubMed: 34715459
Acidosis-induced activation of distal nephron principal cells triggers Gdf15 secretion and adaptive proliferation of intercalated cells [ Acta Physiol (Oxf), 2021, 10.1111/apha.13661]	PubMed: 33840159
Disruption of Her2-Induced PD-L1 Inhibits Tumor Cell Immune Evasion in Patient-Derived Gastric Cancer Organoids [ Cancers (Basel), 2021, 13(24)6158]	PubMed: 34944780

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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