ツカチニブ

化学名:ツカチニブ

CAS番号.937263-43-9

英語名:Tucatinib

CBNumberCB32616075

MFC26H24N8O2

MW480.52

MOL File937263-43-9.mol

别名

ツカチニブ

N6-(4,4-ジメチル-4,5-ジヒドロ-1,3-オキサゾール-2-イル)-N4-(3-メチル-4-{[1,2,4]トリアゾロ[1,5-a]ピリジン-7-イルオキシ}フェニル)キナゾリン-4,6-ジアミン

ツカチニブ物理性質

比重(密度)	1.41±0.1 g/cm3(Predicted)
貯蔵温度	Store at -20°C
溶解性	DMF:1.0(Max Conc. mg/mL);2.08(Max Conc. mM) DMSO:49.0(Max Conc. mg/mL);101.97(Max Conc. mM) DMSO:PBS (pH 7.2) (1:2):0.33(Max Conc. mg/mL);0.69(Max Conc. mM)
外見	A crystalline solid
酸解離定数(Pka)	6.61±0.70(Predicted)
色	White to yellow
InChIKey	SDEAXTCZPQIFQM-UHFFFAOYSA-N
SMILES	N1=C2C(C=C(NC3=NC(C)(C)CO3)C=C2)=C(NC2=CC=C(OC3C=CN4N=CN=C4C=3)C(C)=C2)N=C1

危険有害性情報のコード(GHS)

ツカチニブ価格

製品番号	包装	価格	製品説明	購入
富士フイルム和光純薬株式会社(wako) W01TRCD449790	2.5mg	￥77600		購入
富士フイルム和光純薬株式会社(wako) W01TRCD449790	25mg	￥603100		購入

ツカチニブ化学特性,用途語,生産方法

効能
抗悪性腫瘍薬
説明
Tucatinib is also known as ARRY-380 or Irbinitinib. ARRY-380 is an orally inhibitor of human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. It selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation. Therefore, ARRY-380 may be an alternative treatmentmethod for the treatment of HER2+ cancers.
特性
Year of discovery: 2006
Year of introduction: 2020
Discovered by: Array BioPharma
Developed by: Array BioPharma
Primary targets: HER2
Binding type: I/II
Class: receptor tyrosine kinase
Treatment: HER2-positive breast cancer
Other names: ONT-380, ARRY-380
Oral bioavailability = not reported
Elimination half-life = 5.4 hours
Protein binding = 97%
使用
Tucatinib, a highly selective HER2 inhibitor, was approved in 2020 as a combination therapy with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
brand name
Tukysa^TM
副作用
Tukysa (tucatinib) is a brand-name prescription medication. The Active ingredient is tucatinib. Serious side effects can include diarrhoea, liver damage, and allergic reactions. Mild side effects can occur with Tukysa use. This list doesn’t include all possible mild side effects of the drug. Mild side effects that have been reported with Tukysa include nausea and vomiting, fatigue, reduced appetite, weight loss, joint pain; peripheral neuropathy (nerve damage that causes tingling, numbness, or weakness in your arms, hands, legs, or feet); abdominal pain; headache; skin rash; nosebleeds; anemia (low level of red blood cells); stomatitis; hand-foot syndrome.
Mode of action
Tucatinib binds to tyrosine kinase (an enzyme) of HER2, reducing PI3-kinase and MAP-kinase signaling. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone.
参考文献
[1] PATRICE A LEE. In VivoActivity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with Trastuzumab, Docetaxel or Bevacizumab.[J]. Cancer research, 2009, 69 1: 5104-5104. DOI:10.1158/0008-5472.SABCS-09-5104.
[2] S. MOULDER. Abstract A143: ARRY-380, a selective HER2 inhibitor: From drug design to clinical evaluation.[J]. Molecular Cancer Therapeutics, 2011, 10 1. DOI:10.1158/1535-7163.TARG-11-A143.
[3] V. DINKEL. Abstract 852: ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice[J]. Cancer research, 2012, 72 1: 852-852. DOI:10.1158/1538-7445.AM2012-852.
[4] KOCIE?SKI P. Synthesis of Tucatinib[J]. Synfacts, 2019, 24 1: 0965. DOI:10.1055/s-0039-1690496.
[5] RASHMI K MURTHY. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.[J]. New England Journal of Medicine, 2020, 382 7: 597-609. DOI:10.1056/NEJMoa1914609.
[6] RASHMI MURTHY. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study.[J]. Lancet Oncology, 2018: 880-888. DOI:10.1016/S1470-2045(18)30256-0.

ツカチニブ上流と下流の製品情報

ツカチニブ生産企業

ツカチニブスペクトルデータ(¹HNMR)

937263-43-9, ツカチニブキーワード

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ツカチニブ

危険有害性情報のコード(GHS)

ツカチニブ 価格

ツカチニブ 化学特性,用途語,生産方法

ツカチニブ 上流と下流の製品情報

ツカチニブ 生産企業

ツカチニブ スペクトルデータ(1HNMR)

937263-43-9, ツカチニブ キーワード

ツカチニブ価格

ツカチニブ化学特性,用途語,生産方法

ツカチニブ上流と下流の製品情報

ツカチニブ生産企業

ツカチニブスペクトルデータ(¹HNMR)

937263-43-9, ツカチニブキーワード