Cediranib (AZD2171)

Catalog No.S1017 Batch:S101702

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Technical Data

Formula

C25H27FN4O3
Molecular Weight 450.51 CAS No. 288383-20-0
Solubility (25°C)* In vitro DMSO 90 mg/mL (199.77 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Cediranib (AZD2171, NSC-732208) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3 in HUVEC cells. Cediranib (AZD2171) induces autophagic vacuole accumulation. Phase 3.
Targets
VEGFR2/KDR [1]
(HUVECs)		 c-Kit [1]
(HUVECs)		 VEGFR3/FLT4 [1]
(HUVECs)		 VEGFR1/FLT1 [1]
(HUVECs)		 PDGFRβ [1]
(HUVECs)		 View More
0.5 nM 2 nM <=3 nM 5 nM 5 nM
In vitro 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 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]

Protocol (from reference)

Kinase Assay:[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.

Cell Assay:[1]
  • Cell lines

    HUVEC cell line

  • Concentrations

    10 μM

  • Incubation Time

    72 hours

  • Method

    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.

Animal Study:[1]
  • Animal Models

    PC-3, Calu-6, SKOV-3, MDA-MB-231, and SW620 tumors in female nude (nu/nu genotype) mice

  • Dosages

    0.75-6 mg/kg/day

  • Administration

    Orally

Customer Product Validation

Data from [Data independently produced by Clin Cancer Res, 2014, 20, 3849-61]

Data from [Data independently produced by Neuro Oncol, 2013, 15, 1673-83]

Data from [Data independently produced by Neuro Oncol, 2013, 15, 1673-83]

Data from [J Pharmacol Exp Ther, 2012, 341, 386-395 ]

Selleck's Cediranib (AZD2171) has been cited by 74 publications

Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway [ Front Oncol, 2024, 14:1302850] PubMed: 38420012
WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma [ Cell Oncol (Dordr), 2023, 46(2):391-407] PubMed: 36539575
WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma [ Cell Oncol (Dordr), 2023, 46(2):391-407] PubMed: 36539575
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma [ Biochem Pharmacol, 2023, 214:115681] PubMed: 37429423
Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs [ Int J Mol Sci, 2023, 24(9)8037] PubMed: 37175742
Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib [ Cancers (Basel), 2023, 10.3390/cancers15153919] PubMed: 37568736
Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer [ Braz J Med Biol Res, 2023, 55:e12206] PubMed: 36629522
Development of an in-vitro high-throughput screening system to identify modulators of genitalia development [ PNAS Nexus, 2023, 2(1):pgac300] PubMed: 36712925
A community challenge for a pancancer drug mechanism of action inference from perturbational profile data [ Cell Rep Med, 2022, 3(1):100492] PubMed: 35106508
The multi-kinase inhibitor afatinib serves as a novel candidate for the treatment of human uveal melanoma [ Cell Oncol (Dordr), 2022, 45(4):601-619] PubMed: 35781872

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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