Lenvatinib

別名：E7080

製品コード：S1164 純度：99.97%

レンバチニブ (Lenvatinib (E7080)) はマルチターゲット阻害剤の一種であり、主に VEGFR2(KDR)/VEGFR3(Flt-4) に対して活性を示し IC50 は 4 nM/5.2 nMである一方、VEGFR1/Flt-1に対しては活性が弱く、cell-free assay において FGFR1, PDGFRα/βよりも VEGFR2/3 に対して 10 倍高い選択性を示します。レンバチニブ (E7080) はまた FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET) も阻害し、強力な抗腫瘍活性を呈します。

CAS No. 417716-92-8

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫なし(納期7~10日)
5mg	JPY 22500	国内在庫あり
10mg	JPY 40500	国内在庫あり
50mg	JPY 115500	国内在庫あり
1g	JPY 295500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（116）

製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

Lenvatinib関連製品

関連ターゲット	VEGFR1 VEGFR2 VEGFR3	もっと見る
関連製品	Cediranib (AZD2171) Vatalanib (PTK787) 2HCl Linifanib (ABT-869) Anlotinib (AL3818) dihydrochloride SAR131675 Apatinib Apatinib (YN968D1) mesylate Ki8751 ZM 323881 HCl Semaxanib (SU5416) SU5402 Cediranib Maleate Motesanib Diphosphate (AMG-706) Brivanib (BMS-540215) Motesanib (AMG-706) ZM 306416 KRN 633 Telatinib Fruquintinib SKLB1002 Taxifolin (Dihydroquercetin) BAW2881 (NVP-BAW2881) SU14813 SU1498 SU5614 SKLB 610 Brivanib Alaninate (BMS-582664) SU5408 SU5204	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

VEGFRシグナル伝達経路

VEGFR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
HT29 cells	Cytotoxicity assay	25, 50 nM	72 h	cytotoxic dose: 50 nM and noncytotoxic dose: 25 nM	24815456
ATC cells	Function assay	1, 25 and 50 μM	72 h	Phosphorylated/non-phosphorylated Akt or ERK1/2 proteins (evaluated by ELISA) in lenvatinib-treated samples were significantly reduced in ATC cell cultures.	29517103
TPC-1 and K1 cells	Function assay	50 μM	24 h	The inhibitory effects of lenvatinib on the viability of both cell lines were not influenced by the leptin treatment.	30906321
DX3 and U2OS cells	Function assay	1 μM and 10 μM	16 hours	Lenvatinib inhibit tumor cells migration and invasion at concentrations that both inhibit its known targets and are achievable clinically.	21781317
HCC cell lines Hep3B2.1-7, HuH-7, and JHH-7	Proliferation assay		6 days	Lenvatinib showed selective and potent antiproliferative activity against the HCC cell lines Hep3B2.1‐7, HuH‐7, and JHH‐7, with IC50 values of 0.23, 0.42, and 0.64 μmol/L, respectively.	29733511
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

RET ^[4]	VEGFR2/KDR ^[1] (Cell-free assay)	VEGFR3/FLT4 ^[1] (Cell-free assay)	VEGFR1/FLT1 ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	もっとクリックする
	4.0 nM	5.2 nM	22 nM	39 nM	もっとクリックする

In Vitro
In vitro	E7080, as a potent inhibitor of in vitro angiogenesis, shows a significantly inhibitory effect on VEGF/KDR and SCF/Kit signaling. According to the in vitro receptor tyrosine and serine/threonine kinase assays, E7080 inhibits Flt-1, KDR, Flt-4 with IC50 of 22, 4.0 and 5.2 nM, respectively. In addition to these kinases, E7080 also inhibits FGFR1 and PDGFR tyrosine kinases with IC50 value of 46, 51 and 100 nM for FGFR1, PDGFRα and PDGFRβ, respectively. ^[1] E7080 potently inhibits phosphorylation of VEGFR2 (IC50, 0.83 nM) and VEGFR3 (IC50, 0.36 nM) in HUVECs which is stimulated by VEGF and VEGF-C, respectively. ^[2] A recent study shows that E7080 treatment (both at 1 μM and 10 μM) results in a significant inhibition of cell migration and invasion by inhibiting FGFR and PDGFR signaling. ^[3]
Kinase Assay	In vitro kinase assay ^[1]
Kinase Assay	Tyrosine kinase assays are performed by HTRF (KDR, VEGFR1, FGFR1, c-Met, EGFR) and ELISA (PDGFRβ), using the recombinant kinase domains of receptors. In both assays, 4 μL of serial dilutions of E7080 are mixed in a 96-well round plate with 10 μL of enzyme, 16 μL of poly (GT) solution (250 ng) and 10 μL of ATP solution (1 μM ATP) (final concentration of DMSO is 0.1%). In wells for blanks, no enzyme is added. In control wells no test article is added. The kinase reaction is initiated by adding ATP solution to each well. After 30-minute incubation at 30°C, the reaction is stopped by adding 0.5 M EDTA (10 μL/well) to the reaction mixture in each well. Dilution buffer adequate to each kinase assay is added to the reaction mixture. In the HTRF assay, 50 μL of the reaction mixture is transferred to a 96-well 1/2 area black EIA/RIA plate, HTRF solution (50 μL/well) is added to the reaction mixture, and then kinase activity is determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wavelengths of 620 and 665 nm. In the ELISA, 50 μL of the reaction mixture is incubated in avidin coated 96-well polystyrene plates at room temperature for 30 minutes. After washing with wash buffer, PY20-HRP solution (70 μL/well) is added and the reaction mixture is incubated at room temperature for 30 minutes. After washing with wash buffer, TMB reagent (100 μL/well) is added to each well. After several minutes (10–30 minutes), 1 M H₃PO₄ (100 μL/well) is added to each well. Kinase activity is determined by measurement of absorbance at 450 nm with a microplate reader.
細胞実験	細胞株	HUVECs
	濃度	0-10 μM
	反応時間	72 hours
	実験の流れ	HUVECs (1,000 cells in each well in serum-free medium containing 2% fetal bovine serum) and L6 rat skeletal muscle myoblasts (5,000 cells in each well in serum-free DMEM) are dispensed in a 96-well plate and incubated overnight. E7080 and either VEGF (20 ng/mL) or FGF-2 (20 ng/mL) containing 2% fetal bovine serum and PDGFβ (40 ng/mL) are added to each well. Cells are incubated for 3 days and then the ratios of surviving cells are measured by WST-1 reagent. For proliferation assay, samples are duplicated and three separate experiments are done.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	phospho-FGFR1 / FGFR1 /phospho-FRS2 / FRS2 / phospho-MEK / phospho-ERK phospho-RET Ki-67 / Cyclin D1 / CDK4 / p21 / p53 / Apaf-1 / p-NFκB / Bcl-2 / Cleaved-caspase 3 β-catenin Vimentin / E-cadherin / Snail / Zeb1		25295214
	Growth inhibition assay	Cell viability		25425971

In Vivo
In Vivo	When orally administrated in a H146 xenograft model, E7080 inhibits the growth of H146 tumor at 30 and 100 mg/kg in a dose-dependent manner and leads to tumor regression at 100 mg/kg. Furthermore, E7080 at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and imatinib treatment. ^[1] E7080 significantly inhibits local tumor growth in a MDA-MB-231 mammary fat pad (m.f.p.) model with RTVs (calculated tumor volume on day 8/tumor volume on day 1) of 0.81, and reduces both angiogenesis and lymphangiogenesis of established metastatic nodules of MDA-MB-231 tumor in the lymph nodes. ^[2]
動物実験	動物モデル	H146 tumor cells are implanted subcutaneously (s.c.) into the flank region of female BALB/c nude mice.
	投与量	≤100 mg/kg
	投与経路	Administered via p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06161558	Not yet recruiting	Neoplasms	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 1
NCT05846724	Not yet recruiting	Kaposi Sarcoma\|Classic Kaposi Sarcoma\|Refractory Kaposi Sarcoma	Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico	February 1 2024	Phase 2
NCT05903833	Not yet recruiting	Recurrent Vulvar Cancer\|Persistent Vulvar Cancer\|Metastatic Vulva Cancer\|Locally Advanced Vulvar Cancer	AGO Research GmbH	January 1 2024	Phase 2
NCT05901194	Not yet recruiting	Hepatocellular Carcinoma Non-resectable	Assistance Publique - Hôpitaux de Paris\|Laboratoire EISAI	June 2023	Phase 1\|Phase 2

参考
[1] Matsui J, et al. Int J Cancer. 2008, 122(3), 664-671. [2] Matsui J, et al. Clin Cancer Res. 2008, 14(17),5459-5465. [3] Glen H, et al. BMC Cancer. 2011, 11, 309. [4] Ana M Molina, et al. Cancer Chemother Pharmacol . 2014 Jan;73(1):181-9. + 展開

参考

[4] Ana M Molina, et al. Cancer Chemother Pharmacol . 2014 Jan;73(1):181-9.

+ 展開

化学情報

分子量	426.85	化学式	C₂₁H₁₉ClN₄O₄
CAS No.	417716-92-8	SDF	Download Lenvatinib SDFをダウンロードする
Smiles	COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 20 mg/mL ( (46.85 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo Batch: Add solvents to the product individually and in order.					投与溶液組成計算機
	Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	1.05mg/ml (2.46mM)	Taking the 1 mL working solution as an example, add 50 μL 21 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.5mg/ml (1.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	0.4mg/ml (0.94mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.5mg/ml (5.86mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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