Lenvatinib (E7080) 化学構造
分子量: 426.85

高品質保証

カスタマーフィードバック(3)

Quality Control & MSDS

製品説明

  • Compare VEGFR Inhibitors
    VEGFR製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 Lenvatinib (E7080)は、VEGFR2とVEGFR3のマルチ目標とされたキナーゼ阻害剤で、IC50 がそれぞれ 4 nM と 5.2 nMです。
ターゲット VEGFR2 VEGFR3 VEGFR1 FGFR1 PDGFRα PDGFRβ
IC50 4 nM 5.2 nM 22 nM [1] 46 nM [1] 51 nM [1] 39 nM [1]
In vitro試験 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]
In vivo試験 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]
臨床試験 E7080 is currently in Phase I clinical trials in patients with Refractory Solid Tumors Lymphomas.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

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.

細胞アッセイ: [2]

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.

動物実験: [1]

動物モデル H146 tumor cells are implanted subcutaneously (s.c.) into the flank region of female BALB/c nude mice.
製剤 E7080 is dissolved in suspended in 0.5% methylcellulose.
投薬量 ≤100 mg/kg
投与方法 Administered via p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Lenvatinib (E7080) SDF
分子量 426.85
化学式

C21H19ClN4O4

CAS No. 417716-92-8
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 40 mg/mL warmed (93.7 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose 30 mg/mL
* <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.
化学名 1-(4-(6-carbamoyl-7-methoxyquinolin-4-yloxy)-2-chlorophenyl)-3-cyclopropylurea

カスタマーフィードバック (3)


Click to enlarge
Rating
Source Asian Pac J Cancer Prev, 2014, 15(7), 3113-21. Lenvatinib (E7080) purchased from Selleck
Method Annexin V-FITC assay
Cell Lines HT29 cells
Concentrations 12.5, 25, 50 nM
Incubation Time
Results The apoptosis induction was assessed by Annexin V-FITC assay. In the dot plot of flow cytometric analysis, the lower-right (LR) area was the Annexin V positive/PI negative portion which represented the preapoptotic fraction, the upper-right (UR) area was the Annexin V positive/PI positive portion which represented the apoptotic fraction. The agents DuP-697 +E7080 combinations at 50+50, 25+25 and 12.5+12.5 nM showed strong concentration dependent apoptotic effect. The percentage of UR (apoptosis portion) area was 78.4%, 67.3% and 33.4% respectively.

Click to enlarge
Rating
Source Chin J Cancer Res, 2013, 25(5), 572-84. Lenvatinib (E7080) purchased from Selleck
Method RTCA
Cell Lines HT29 cells
Concentrations 6.25-100 nM
Incubation Time 12, 24, 36 h
Results E7080 treated HT29 cells exhibited decreasing CI values in a concentration-dependent manner. While 100 nmol/L has shown complete cytotoxic effect and decreased CI to 0.1, 50 nmol/L decreased CI to 0.4. Both showed statistically significant cytotoxic effect when compared with the control (P<0.05).

Click to enlarge
Rating
Source Chin J Cancer Res, 2013, 25(5), 572-84. Lenvatinib (E7080) purchased from Selleck
Method RTCA
Cell Lines HT29 cells
Concentrations
Incubation Time 24 h
Results Twenty-four hours after treatment with E7080, the IC50 of 5.60×10-8 mol/L was achieved. Calculation of IC50 of E7080 (IC50 =5.60×10–8 mol/L, square R =0.998).

文献中の引用 (5)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related VEGFR 阻害剤

  • SU5402

    SU5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC50 of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGF-Rβ, respectively.

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • R428 (BGB324)

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • Pexidartinib (PLX3397)

    Pexidartinib (PLX3397) is an oral, potent mutil-targeted receptor tyrosine kinase inhibitor of CSF-1R, Kit, and Flt3 with IC50 of 20 nM, 10 nM and 160 nM, respectively. Phase 3.

  • Regorafenib (BAY 73-4506)

    Regorafenib (BAY 73-4506)は、VEGFR1、VEGFR2、VEGFR3、PDGFRβ、キット、RET</b、Raf-1のためのマルチターゲット阻害剤で 、 IC50がそれぞれ13 nM、4.2 nM、46 nM、 22 nM、 7 nM、 1.5 nM 、2.5 nMです。

  • Axitinib

    Axitinibは、マルチターゲット阻害剤で、 VEGFR1VEGFR2VEGFR3、 PDGFRβ 、c-Kit に作用する時、IC50 がそれぞれ 0.1 nM、0.2 nM、0.1-0.3 nM、 1.6 nM 、1.7 nMになる。

    Features:Superior as second-line therapy relative to sorafenib (current standard-of-care).

  • Cabozantinib (XL184, BMS-907351)

    Cabozantinib (XL184, BMS-907351)は、VEGFR2とc-Metの強力な幅広いスペクトル・チロシン・キナーゼ阻害剤で、 IC50 がそれぞれ 0.035 nM と 1.3 nMです。

  • Nintedanib (BIBF 1120)

    Nintedanib (BIBF 1120)は三重血管キナーゼ阻害剤、VEGFR1, VEGFR2, VEGFR3 を作用すると、 IC50 がそれぞれ 34 nM, 5 nM 、 5 nMとなる。Phase 2.

  • Vandetanib (ZD6474)

    Vandetanib (ZD6474)は、VEGFR2の強力な阻害剤で、IC50 が 40 nM。

最近チェックしたアイテム

Tags: Lenvatinib (E7080)を買う | Lenvatinib (E7080)供給者 | Lenvatinib (E7080)を購入する | Lenvatinib (E7080)費用 | Lenvatinib (E7080)生産者 | オーダーLenvatinib (E7080) | Lenvatinib (E7080)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID