Cediranib (AZD2171, RECENTIN)

Agent Description

Cediranib is a potent small molecule vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor of all three VEGF receptors (VEGFR-1, 2 and 3) at nanomolar concentrations. The Chemical name is 4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy] quinazoline maleate with a molecular mass of 566.59 as maleate salt (450.52 as free base). Cediranib tablets contain cediranib maleate, mannitol, dibasic calcium phosphate anhydrous, sodium starch glycolate, microcrystalline cellulose and magnesium stearate with a film coat containing hypromellose 2910, polyethylene glycol 400, red iron oxide, yellow iron oxide, black iron oxide and titanium dioxide.

Mechanism of Action

Cediranib is a potent VEGF receptor tyrosine kinase (RTK) inhibitor of all three VEGF Receptors (VEGFR-1, 2 and 3). Inhibition of VEGF signaling leads to the inhibition of angiogenesis, lymphangiogenesis, neo-vascular survival and vascular permeability. Cediranib also inhibits c-Kit tyrosine kinase based on steady-state free plasma concentrations achieved with 20 mg once daily in patients.

Classification

VEGF RTK inhibitor of VEGFR-1, 2, and 3

Molecular Targets

VEGFR-1, VEGFR-2, VEGFR-3, c-Kit

Monograph

On-going clinical trials for cediranib are listed on https://clinicaltrials.gov. Cediranib inhibited the growth of tumors in preclinical models in a dose-dependent manner. A reduction in micro-vessel density and metastasis was also observed in these preclinical models. Collectively, these changes indicate that cediranib limits tumor growth, metastases and microvascular permeability. Cediranib is not approved in any territory. Currently cediranib is being studied in phase III trials in combination with olaparib in patients with relapsed ovarian cancer. Phase II trials for the combination of cediranib and olaparib are also ongoing in other malignancies. Earlier phase I/II trials are ongoing for the combination of cediranib and durvalumab +/- olaparib.

Studies of Interest

N/A

Information collaborator would like included in investigator proposals

Cediranib will be available via the NCI Formulary for non-clinical studies only