Home Protein Tyrosine Kinase VEGFR inhibitor E7080 (Lenvatinib)

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E7080 (Lenvatinib) VEGFR inhibitor

제품 번호: S1164

Lenvatinib is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3.
E7080 (Lenvatinib) VEGFR inhibitor Chemical Structure

화학 구조

분자량: 426.85

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

함께 자주 사용되는 제품 E7080 (Lenvatinib)

Padnarsertib (KPT-9274, ATG-019)

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

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
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
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
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
HT29 cells Cytotoxicity assay 25, 50 nM 72 h cytotoxic dose: 50 nM and noncytotoxic dose: 25 nM 24815456
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
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 426.85 화학식

C21H19ClN4O4

 보관 (수령일로부터)
CAS 번호 417716-92-8 SDF 다운로드 원액 보관

동의어 E7080 Smiles COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl

용해도 (Solubility)

In vitro
배치:

DMSO : 20 mg/mL (46.85 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
RET
VEGFR2/KDR
(Cell-free assay)
4.0 nM
VEGFR3/FLT4
(Cell-free assay)
5.2 nM
VEGFR1/FLT1
(Cell-free assay)
22 nM
PDGFRβ
(Cell-free assay)
39 nM
FGFR1
(Cell-free assay)
46 nM
PDGFRα
(Cell-free assay)
51 nM
Kit
(Cell-free assay)
100 nM
시험관 내(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, this compound inhibits Flt-1, KDR, Flt-4 with IC50 of 22, 4.0 and 5.2 nM, respectively. In addition to these kinases, this compound also inhibits FGFR1 and PDGFR tyrosine kinases with IC50 value of 46, 51 and 100 nM for FGFR1, PDGFRα and PDGFRβ, respectively. This compound 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. A recent study shows that this compound treatment (both at 1 μM and 10 μM) results in a significant inhibition of cell migration and invasion by inhibiting FGFR and PDGFR signaling.

키나아제 분석
In vitro 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 this compound 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.
생체 내(In vivo)

When orally administrated in a H146 xenograft model, Lenvatinib (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, this compound at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and imatinib treatment. It 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.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/24190702/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Vimentin / E-cadherin / Snail / Zeb1 β-catenin Ki-67 / Cyclin D1 / CDK4 / p21 / p53 / Apaf-1 / p-NFκB / Bcl-2 / Cleaved-caspase 3 phospho-RET phospho-FGFR1 / FGFR1 /phospho-FRS2 / FRS2 / phospho-MEK / phospho-ERK
S1164-WB4
30286728
Growth inhibition assay Cell viability
S1164-viability
25425971

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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