Lenvatinib

別名:E7080

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。

Lenvatinib化学構造

CAS No. 417716-92-8

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

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(107)

製品安全説明書

現在のバッチを見る: 純度: 99.97%
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Lenvatinibと併用されることが多い化合物

Paclitaxel


Lenvatinib and Paclitaxel combination exhibit antiproliferative effects and inhibit tumor growth in nude mice with anaplastic thyroid cancer (ATC).


Desidero TD, et al. Pharmacol Res. 2020 Aug;158:104920.

Cabozantinib (XL184)


Lenvatinib and Cabozantinib combination exerts immunomodulatory effects in the treatment of hepatocellular carcinoma (HCC).


Chen R, et al. Cancer Cell Int. 2022 Feb 11;22(1):73.

Axitinib


Lenvatinib and Axitinib combination is approved as second-line agents in the treatment of renal cell carcinoma (RCC).


Venur VA, et al. Drug Des Devel Ther. 2017 Apr 11;11:1175-1182.

Selinexor (KPT-330)


Lenvatinib and Selinexor combination exhibit superior anti-tumor activity in anaplastic thyroid cancer cells (8505C) subcutaneous xenografts.


Khan HY, et al. Int J Mol Sci. 2019 Dec 29;21(1):237.

KPT 9274 (ATG-019)


Lenvatinib and KPT 9274 combination exhibit superior anti-tumor activity in anaplastic thyroid cancer cells (8505C) subcutaneous xenografts.


Khan HY, et al. Int J Mol Sci. 2019 Dec 29;21(1):237.

Lenvatinib関連製品

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 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。
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)
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4.0 nM 5.2 nM 22 nM 39 nM
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]
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
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
NCT06161558 Not yet recruiting
Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
January 12 2024 Phase 1
NCT05901194 Not yet recruiting
Hepatocellular Carcinoma Non-resectable
Assistance Publique - Hôpitaux de Paris|Laboratoire EISAI
June 2023 Phase 1|Phase 2
NCT05733715 Recruiting
Renal Cell Carcinoma
Abramson Cancer Center at Penn Medicine|Merck Sharp & Dohme LLC
May 3 2023 Early Phase 1
NCT05433116 Recruiting
Head and Neck Squamous Cell Carcinoma
Universität des Saarlandes
May 25 2023 Phase 2

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

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

実験計算

モル濃度計算器

質量 濃度 体積 分子量

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)

mg/kg g μL

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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Tags: Lenvatinibを買う | Lenvatinib ic50 | Lenvatinib供給者 | Lenvatinibを購入する | Lenvatinib費用 | Lenvatinib生産者 | オーダーLenvatinib | Lenvatinib化学構造 | Lenvatinib分子量 | Lenvatinib代理店