Tucatinib

製品コードS8362 バッチS836202

化学情報

	Synonyms	Irbinitinib, ONT-380, ARRY-380	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₆H₂₄N₈O₂
	分子量	480.52	CAS No.	937263-43-9
Solubility (25°C)*	体外	DMSO	96 mg/mL (199.78 mM)
		Ethanol	21 mg/mL (43.7 mM)
		Water	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	Tucatinib (Irbinitinib, ONT-380, ARRY-380) is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity.
in vitro	The compound is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in both in vitro and in cell-based assays^[1]. In cell-based assays, ARRY-380 is ~500-fold selective for HER2 vs. EGFR and is equipotent against truncated p95-HER2^[2].
in vivo	In vivo, ARRY-380 significantly inhibits tumor growth in multiple HER2-dependent tumor xenograft models^[2]. It shows excellent activity in numerous mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. In the BT-474 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size)^[1].

製品説明

Tucatinib (Irbinitinib, ONT-380, ARRY-380) is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity.

in vitro

The compound is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in both in vitro and in cell-based assays^[1].

In cell-based assays, ARRY-380 is ~500-fold selective for HER2 vs. EGFR and is equipotent against truncated p95-HER2^[2].

in vivo

In vivo, ARRY-380 significantly inhibits tumor growth in multiple HER2-dependent tumor xenograft models^[2].

It shows excellent activity in numerous mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. In the BT-474 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size)^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	ZR75.1, SKBR3, BT474 and NZBR3 cells
	濃度	380 μM
	反応時間	24 h
	実験の流れ	Cells were treated with ARRY-380 for 24 h.
動物実験	動物モデル	Nude mice
	投薬量	ranging up to 200 mg/kg/d
	投与方法	p.o.

参考

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：

HER4 and EGFR activate cell signaling in NRG1 fusion-driven cancers: implications for HER2/HER3-specific vs. pan-HER targeting strategies [ J Thorac Oncol, 2023, S1556-0864(23)00802-X]	PubMed: 37678511
Irreversible HER2 inhibitors overcome resistance to the RSL3 ferroptosis inducer in non-HER2 amplified luminal breast cancer [ Cell Death Dis, 2023, 14(8):532]	PubMed: 37596261
Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer [ Cancers (Basel), 2023, 15(4)1216]	PubMed: 36831558
Drug-drug interaction potentials of tucatinib inhibition of human UDP-glucuronosyltransferases [ Chem Biol Interact, 2023, 381:110574]	PubMed: 37263554
Novel HER2-targeted therapy to overcome trastuzumab resistance in HER2-amplified gastric cancer [ Sci Rep, 2023, 13(1):22648]	PubMed: 38114573
High-throughput screen in vitro identifies dasatinib as a candidate for combinatorial treatment with HER2-targeting drugs in breast cancer [ PLoS One, 2023, 18(1):e0280507]	PubMed: 36706086
Metabolic diversity within breast cancer brain-tropic cells determines metastatic fitness [ Cell Metab, 2022, 34(1):90-105.e7]	PubMed: 34986341
Poziotinib Inhibits HER2-Mutant-Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer [ Cancer Res, 2022, 82(16):2928-2939]	PubMed: 35736563
Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation [ Front Pharmacol, 2022, 13:1032975]	PubMed: 36313330
miR-101-5p Acts as a Tumor Suppressor in HER2-Positive Breast Cancer Cells and Improves Targeted Therapy [ Breast Cancer (Dove Med Press), 2022, 14:25-39]	PubMed: 35256859

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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