Cediranib (AZD2171) inhibited VEGFR2 and KDR phosphorylation with IC50s of 0.4 and 0.5 nM, respectively. Cediranib significantly increased survival of mice wth glioblastoma by decreasing tumor vessel permeability, normalizing perivascular cell coverage, and thinning of the basement membrane, thus controlling edema. Cediranib demonstrated potent antitumor and antiangiogenic efficacy in the murine renal cell carcinoma model.
|Cell lines||HUVEC cells line|
|Preparation method||Inhibition of growth factor–mediated cellular proliferation.
HUVEC proliferation in the presence and absence of growth factors was evaluated following a 4-day incubation by 3H-thymidine incorporation, as described previously. Proliferation of MG63 osteosarcoma cells was induced by PDGF-AA, which selectively activates PDGFR-α homodimer signaling. Cells were cultured in DMEM without phenol red (Sigma-Aldrich) containing 1% charcoal stripped FCS, 2 mmol/L glutamine, and 1% nonessential amino acids (Invitrogen, Paisley, United Kingdom) for 24 hours. AZD2171 or vehicle was added with PDGF-AA ligand (50 ng/mL; Sigma-Aldrich) and plates reincubated for 72 hours. Cellular proliferation was determined using a bromodeoxyuridine ELISA (Roche Diagnostics Ltd., Lewes, United Kingdom).
|Concentrations||0~10 μ M|
|Incubation time||72 h|
|Animal models||female Alderley Park mice or rat bearing human tumor xenografts model|
|Formulation||suspended in 1% (w/v) aqueous polysorbate 80 (polyoxyethylene; sorbitan mono-oleate in deionized water)(mice) / 0.5% (w/v) hydroxypropyl methylcellulose solution containing 0.1% (w/v) aqueous polysorbate 80(rat)|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
Cediranib Plus FOLFOX/CAPOX Versus Placebo Plus FOLFOX/CAPOX in Patients With Previously Untreated Metastatic Colorectal Cancer: A Randomized, Double-Blind, Phase III Study (HORIZON II).
Hoff et al. J Clin Oncol. 2012 Sep 10. PMID: 22965965.
Cediranib With mFOLFOX6 Versus Bevacizumab With mFOLFOX6 As First-Line Treatment for Patients With Advanced Colorectal Cancer: A Double-Blind, Randomized Phase III Study (HORIZON III).
Schmoll et al. J Clin Oncol. 2012 Sep 10. PMID: 22965961.
Advanced Solid Tumors Treated with Cediranib: Comparison of Dynamic Contrast-enhanced MR Imaging and CT as Markers of Vascular Activity.
Messiou et al. Radiology. 2012 Aug 13. PMID: 22891356.
Cediranib in patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium.
Campbell et al. Lung Cancer. 2012 Jul 23. PMID: 22831987.
Cediranib: a VEGF receptor tyrosine kinase inhibitor.
Sahade et al. Future Oncol. 2012 Jul;8(7):775-81. PMID: 22830398.
Response of HT29 colorectal xenograft model to cediranib assessed with (18) F-fluoromisonidazole positron emission tomography, dynamic contrast-enhanced and diffusion-weighted MRI.
Bokacheva et al. NMR Biomed. 2012 Jul 8. PMID: 22777834.
AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer.
Wedge SR, et al. Cancer Res. 2005 May 15;65(10):4389-400. PMID: 15899831.
|Related VEGFR/PDGFR Products|
|EG00229 Trifluoroacetate salt
EG00229 Trifluoroacetate is the first small molecule inhibitor of the neuropilin-1 and VEGF-A interaction with an IC50 of inhibition of 8 uM (125I-VEGF binding to PAE/NRP1 cells).
Apatinib is a selective VEGFR2 inhibitor with IC50 of 1 nM.
JI-101 is an orally available multi-kinase inhibitor of VEGFR2，PDGFRβ and EphB4 with potential antiangiogenic and antineoplastic activities.
BAW2881 (NVP-BAW2881) is a potent and selective VEGFR2 inhibitor with activity to inhibit chronic and acute skin inflammation.
SU 1498 is a selective inhibitor of the receptor tyrosine kinase VEGF receptor 2 (VEGFR2, aka FLK1; IC50 = 700 nM).
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