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受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
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Synonyms | ZD6474 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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| 化学式 | C22H24BrFN4O2 |
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| 分子量 | 475.35 | CAS No. | 443913-73-3 | ||||
| Solubility (25°C)* | 体外 | DMSO | 4 mg/mL (8.41 mM) | ||||
| Water | Insoluble | ||||||
| Ethanol | Insoluble | ||||||
| 体内 （毎回新しく調製した物を用意してください） |
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | バンデタニブは、細胞フリーアッセイにおいてIC50が40 nMの強力なVEGFR2阻害剤です。また、VEGFR3とEGFRもそれぞれIC50が110 nMおよび500 nMで阻害します。PDGFRβ、Flt1、Tie-2、FGFR1には感受性がなく、IC50は1.1-3.6 μMです。MEK、CDK2、c-Kit、erbB2、FAK、PDK1、Akt、IGF-1Rに対しては10 μMを超えるIC50で活性がありません。バンデタニブ（ZD6474）は、reactive oxygen species (ROS)のレベルを上昇させることにより、apoptosisを増加させ、autophagyを誘導します。 |
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| in vitro | Vandetanib also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. This compound is not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM, while almost has no activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. It inhibits VEGF-, EGF- and bFGF-stimulated HUVEC proliferation with IC50 of 60 nM, 170 nM and 800 nM, with no effect on basal endothelial cell growth. This chemical inhibits tumor cell growth with IC50 of 2.7 μM (A549) to 13.5 μM (Calu-6). It displays an inhibitory effect on the basal ABCG2-ATPase. Parental and ABCG2-expressing A431 cells showed similar sensitivities toward this compound. Exposure to EGFR inhibitors decreases pEGFR levels in A431 cells, with this compound displaying only a moderate effect. It displays a slight but measurable effect, whereas gefitinib, pelitinib and neratinib completely inhibit ABCG2-mediated efflux of mitoxantrone from A431/ABCG2 cells, similarly to the specific ABCG2 inhibitor Ko143. It inhibits both PC3wt and PC3R cell lines with similar IC50 of 13.3 μM and 11.5 μM, respectively. This chemical suppresses phosphorylation of VEGFR2 in HUVEC and EGFR in hepatoma cells and inhibits cell proliferation. It causes an accumulation of cells in the G0-G1 phases in GEO and OVCAR-3 cells and increases apoptosis in OVCAR-3, ZR-75-1, MCF-10A ras, and GEO cells. This compound causes a dose-dependent inhibition of EGFR phosphorylation in mouse NIH-EGFR fibroblasts and human MCF-10A ras breast cancer cells, two cell lines that overexpress the human EGFR. It treatment results in a dose-dependent inhibition of soft agar growth in seven human cell lines (breast, colon, gastric, and ovarian) with functional EGFR but lacking VEGFR2. |
| in vivo | Vandetanib (2.5 mg/kg, i.v.), reverses a VEGF-induced hypotension by 63% but does not significantly affect a bFGF-induced hypotension. This compound (100 mg/kg) inhibits the tumor-induced blood vessel formation by 79%. It (12.5-100 mg/kg, orally) shows great tumor growth inhibition in human tumor xenografts including Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung, with little effects on body weight. In PC3wt xenografts, administration of this compound alone exerts paradoxical tumor growth stimulating effects. In PC3R xenografts, the low dose of this chemical (25 mg/kg) has no significant effect relative to control, whereas the high dose (50 mg/kg) significantly inhibits tumor growth compared with control. In contrast, the high-dose combination reveals a significant negative interaction between this compound 50 mg/kg and docetaxel 30 mg/kg in PC3R cells. In tumor-bearing mice, it suppresses phosphorylation of VEGFR2 and EGFR in tumor tissues, significantly decreases tumor vessel density, enhances tumor cell apoptosis, suppresses tumor growth, improves survival, reduces number of intrahepatic metastases, and up-regulates VEGF, TGF-alpha and EGF in tumor tissues. Treatment with this compound is not associated with serious adverse events, including ALT abnormality, bone marrow suppression or body weight loss. This chemical treatment of nude mice bearing palpable GEO colon cancer xenografts (which are sensitive to inhibition of EGFR signaling) induces dose-dependent tumor growth inhibition. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Kinase inhibition | |
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| Vandetanib is incubated with enzyme, 10 mM MnCl2, and 2 μM ATP in 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine is then detected by sequential incubation with a mouse IgG anti-phosphotyrosine 4G10 antibody, a horseradish peroxidase-linked sheep antimouse immunoglobulin antibody, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). This methodology is adapted to examine selectivity versus tyrosine kinases associated with EGFR, PDGFRβ, Tie-2, FGFR1, c-kit, erbB2, IGF-1R, and FAK. All enzyme assays (tyrosine or serine-threonine) used appropriate ATP concentrations at or just below the respective Km (0.2–14 μM). Selectivity versus serine-threonine kinases (CDK2, AKT, and PDK1) is examined using a relevant scintillation proximity-assay (SPA) in 96-well plates. CDK2 assays contained 10 mM MnCl2, 4.5 μM ATP, 0.15 μCi of [γ-33 P]ATP/reaction, 50 mM HEPES (pH 7.5), 1 mM DTT, 0.1 mM sodium orthovanadate, 0.1 mM sodium fluoride, 10 mM sodium glycerophosphate, 1 mg/mL BSA fraction V, and a retinoblastoma substrate (part of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μM final concentration). Reactions are allowed to proceed at room temperature for 60 minutes before quenching for 2 hours with 150 μL of a solution containing EDTA (62 mM final concentration), 3 μg of a rabbit immunoglobulin anti-glutathione S-transferase antibody and protein A SPA-polyvinyltoluene beads (0.8 mg/reaction). Plates are then sealed, centrifuged (1200× g for 5 minutes), and counted on a Microplate scintillation counter for 30 seconds. | ||
| 細胞アッセイ | 細胞株 | Calu-6, PC-3, MDA-MA-231, SKOV-3, SW620, A549, A431, B16-F10(AP3) and Lewis Lung cells |
| 濃度 | 0.1–100 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | Tumor cells are plated in their respective media at predetermined densities that are known to enable logarithmic cell growth during the period of assay (PC-3, 500 cells/well; all others, 1000 cells/well). Plates are incubated for 24 hours (37 °C with CO2) before the addition of Vandetanib (0.1–100 μM) or vehicle (0.1% DMSO in medium). Plates are reincubated for an additional 72 hours before assessing cell proliferation by [3 H]thymidine incorporation by a beta counter. |
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| 動物実験 | 動物モデル | Female athymic (nu/nu genotype) Swiss mice with PC-3, Calu-6, SKOV-3, and MDA-MB-231 tumors |
| 投薬量 | 12.5 mg/kg/day, 25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day | |
| 投与方法 | Oral administration | |
参考
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カスタマーフィードバック
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Data from [Hypertension, 2011, 58, 85-92]
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Data from [Hypertension, 2011, 58, 85-92]
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Data from [Hypertension, 2011, 58, 85-92]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability [ Virulence, 2025, 16(1):2489751] | PubMed: 40189910 |
| Kinase Plasticity in Response to Vandetanib Enhances Sensitivity to Tamoxifen in Estrogen Receptor Positive Breast Cancer [ bioRxiv, 2025, 2024.12.19.629395] | PubMed: 39975402 |
| CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT [ Circulation, 2024, 150(7):563-576] | PubMed: 38682330 |
| Novel therapeutic strategies targeting bypass pathways and mitochondrial dysfunction to combat resistance to RET inhibitors in NSCLC [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(6):167249] | PubMed: 38768929 |
| Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] | PubMed: 39319271 |
| Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma [ Front Pharmacol, 2024, 15:1345070] | PubMed: 38799165 |
| ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment [ Cell Rep, 2023, 42(6):112665] | PubMed: 37330911 |
| Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis [ Cell Reports, 2023, 112328] | PubMed: None |
| Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis [ Cell Rep, 2023, 42(4):112328] | PubMed: 37027305 |
| Phosphate-induced activation of VEGFR2 leads to caspase-9-mediated apoptosis of hypertrophic chondrocytes [ iScience, 2023, 26(9):107548] | PubMed: 37636062 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。