Cediranib (AZD2171) 化学構造
分子量: 450.51

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Quality Control & MSDS

製品説明

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製品の説明

生物活性

製品説明 Cediranib(AZD2171)は非常に強力なVEGFR2阻害剤、VEGFを刺激された増殖とKDRリン酸化に作用すると、IC50がそれぞれ0.4nMと0.5nMになる。
ターゲット VEGFR2 Flt1/4
IC50 0.5 nM 5 nM/≤3 nM [1]
In vitro試験 Cediranib inhibits VEGF-stimulated proliferation with IC50 of 0.4 nM. Cediranib suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. Cediranib has been shown to block Flt1-associated kinase with IC50 of 5 nM and VEGF-C and VEGF-D receptor Flt-4 with IC50 less than 3 nM. In addition, the IC50 values for inhibition of c-Kit and PDGFRβ tyrosine kinase are 2 nM and 5 nM respectively. Furthermore, no inhibition of enzyme activity is observed when 10 μM Cediranib is assayed with 100 μM ATP against AMPK, Chk1 Akt/PKB and others. Micromolar concentrations of Cediranib are needed to prevent tumor cell proliferation in vitro. [1]
In vivo試験 Cediranib even suppresses tubule sprouting at subnanomolar concentrations and inhibits VEGF-induced angiogenesis. Cediranib causes hypertrophy in bone growth plate and prevents luteal development in ovary. These are physiological processes that are dependent upon angiogenesis. Cediranib shows broad spectrum activity in human tumor models at doses that are well tolerated. [1] Besides, Cediranib causes regression of vascular tissues in human lung tumor xenografts. [2]
臨床試験 Cediranib is currently being evaluated in a phase II clinical trial for the treatment of advanced solid tumors.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

Kinase inhibition Cediranib is dissolved in DMSO at a concentration of 10 mM. All enzyme assays are run at, or just below, the respective Km for ATP (0.2 - 30 μM). The inhibitory activity of Cediranib is determined against a range of recombinant tyrosine kinases [KDR, Flt-1, Flt-4, c-Kit, PDGFRα, PDGFRβ, CSF-1R, Flt-3, FGFR1, Src, Abl, epidermal growth factor receptor (EGFR), ErbB2, Aurora A, and Aurora B] using ELISA. Selectivity versus CDK2 and CDK4 serine/threonine kinases is examined using scintillation proximity assays with a retinoblastoma substrate and [γ-sup>33P]ATP. Activity of Cediranib is compared to MAPK kinase (MEK), which shows dual specificity. It is determined using a MAPK substrate, [γ-33P]ATP, and paper capture/scintillation counting.

細胞アッセイ: [1]

細胞株 HUVEC cell line
濃度 10 μM
反応時間 72 hours
実験の流れ The proliferation of the HUVEC cell line is evaluated in the presence and absence of growth factors by measuring 3H-thymidine incorporation following a 4-day incubation period. Proliferation of MG63 osteosarcoma cells is induced by PDGF-AA, which selectively activates signaling of the PDGFRα homodimer. HUVEC and MG63 osteosarcoma cells are cultured in DMEM without phenol red containing 1% charcoal stripped FCS, 2 mM glutamine, and 1% nonessential amino acids for 24 hours. Cediranib or vehicle is added with PDGF-AA ligand (50 ng/mL) and plates incubated for another 72 hours. Cellular proliferation is determined using bromodeoxyuridine ELISA.

動物実験: [1]

動物モデル PC-3, Calu-6, SKOV-3, MDA-MB-231, and SW620 tumors in female nude (nu/nu genotype) mice
製剤 Suspended in 1% (w/v) aqueous polysorbate 80
投薬量 0.75-6 mg/kg/day
投与方法 Orally

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 Cediranib (AZD2171) SDF
分子量 450.51
化学式

C25H27FN4O3

CAS No. 288383-20-0
保管 2年-20℃
6月-80℃in solvent
別名 NSC-732208
溶解度 (25°C) * In vitro DMSO 90 mg/mL (199.77 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 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline

カスタマーフィードバック (5)


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Source Clin Cancer Res, 2014, 20, 3849-61. Cediranib (AZD2171) purchased from Selleck
Method Western blot
Cell Lines A549, HCC461, and HCC4006 cells
Concentrations 0, 5 and 10 nM
Incubation Time 48 h
Results It sought to determine whether treatment with AZD2171, a known inhibitor of VEGFR-2 activity, decreases EZH2 expression. When treated A549, HCC461, and HCC4006 cells with different doses of AZD2171 (0, 5, and 10 nM) for 48 hours, it found that this treatment decreased the expression of EZH2 in HCC4006 and HCC461 cells expressing VEGFR-2 but not in A549 cells lacking expression of VEGFR-2 in a dose-dependent manner.

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Source Neuro Oncol, 2013, 15, 1673-83. Cediranib (AZD2171) purchased from Selleck
Method Immunohistochemical staining
Cell Lines Mouse 4C8 glioma cells
Concentrations
Incubation Time
Results Antivascular/antitumor efficacy and effectively slowing tumor growth and extending survival in mouse 4C8 glioma. Histological studies performed after completion of the longitudinal MRI studies confirmed the perfusion MRI results and provided further information regarding tumor pathology. Representative histological tumor sections with CD31 vascular staining are shown in A–D and indicate clearly demarcated tumor vessels (see arrows). Consistent with the perfusion MRI results, it generally observed a greater prevalence of vessels at tumor borders. Multiple vessels are indicated in A–C, in sections from untreated, quinacrine-treated, and cediranib-treated tumors. In contrast, in D, a section from a cediranib/quinacrine-treated tumor shows substantial necrosis (indicated by nonspecific staining) and fewer vessels.

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Source Neuro Oncol, 2013, 15, 1673-83. Cediranib (AZD2171) purchased from Selleck
Method Western blot, VOS fl microscopy
Cell Lines 4C8 cells
Concentrations 2, 2.5, 3 uM
Incubation Time 10, 24, 72h
Results Western blot of LC3 obtained from 4C8 cells grown and exposed to cediranib, quinacrine, or combined cediranib/quinacrine treatment. LC3 comprises both the cytosolic form, LC3-I, and its lipidated form, LC3-II, which is converted from LC3-I and is a well-accepted biomarker of autophagic vacuoles. LC3-II increases are generally indicative of increased autophagic flux and/or late-stage autophagy inhibition(A). Fluorescence microscopy images shows combined cediranib/quinacrine resulted in a strong accumulation of LC3-II and notably in the presence of hypoxia induced the highest levels that were observed(B). While the untreated cells indicate a diffuse RFP-LC3 distribution indicative of cytosolic LC3-I, cells exposed to combined cediranib/quinacrine clearly indicate a punctate distribution, indicative of LC3-II, confirming the increased presence of autophagic vacuoles(C).

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Source J Pharmacol Exp Ther, 2012, 341, 386-395 . Cediranib (AZD2171) purchased from Selleck
Method Accumulation of Probe Substrates
Cell Lines MDL-Transfected Cell/Bcrp1-Transfected Cell
Concentrations 0.1-100 μg/ml
Incubation Time 2 h
Results Increasing concentrations of cediranib enhanced the intracellular accumulation of vinblastine in the MDR1-transfected cells.

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Source Dr. Mikhail Menshikov of Cardiology Research Center. Cediranib (AZD2171) purchased from Selleck
Method Cell viability assay
Cell Lines Ba/F3 cells
Concentrations 0-1000 nM
Incubation Time 72 h
Results Cediranib inhibited the survival of Ba/F3 cell lines expressing the recombinant TEL/kinase domain fusion protein for FGFR1-4 in a dose-dependent manner.

文献中の引用 (17)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
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