Cediranib 是一种可口服的高选择性VEGFR2抑制剂，对FLT1、KDR、FLT4、PDGFRα、PDGFRβ和c-Kit的IC50值分别为小于1、小于3、5、5、36和 2nM。

Cediranib (AZD2171) is a highly potent (IC50< 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro, also inhibits Flt1/4 (IC50: 5 nM/≤3 nM), similar activity against PDGFRβ and c-Kit, selective more for VEGFR than PDGFR-α (36-fold), CSF-1R (110-fold), and Flt3 (1000-fold) in HUVEC cells.

Cediranib对人类移植瘤模型具有十分有效的作用且有剂量依赖性.此外,Cediranib可使人肺癌移植瘤血管衰退.Cediranib使骨骼过度生长,对卵巢中黄体的产生具有阻碍作用,并抑制依赖于血管生成的生理程序.

在体外,Cediranib（微摩）可直接抑制肿瘤细胞增殖。Cediranib（次纳摩）阻断细管产生,且对体内VEGF诱导的血管生成有抑制作用。Cediranib对bFGF（IC50：0.5 μM）和EGF（IC50：0.11 μM）有抑制作用。在MG63细胞系中,Cediranib抑制PDGF-AA（IC50：0.04 μM）。Cediranib抑制 Flt-1相关激酶（IC50：5 nM）,还对VEGF-C和VEGF-D受体Flt-4有抑制作用（IC50<3 nM）。此外,Cediranib对c-Kit（IC50：2 nM）和PDGFR-β（IC50：5 nM）酪氨酸激酶有抑制作用。

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.

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. (Only for Reference)

288383-20-0

C25H27FN4O3

450.514

西地尼布;NSC-732208;AZD2171

H2O:<1 mgml
DMSO:83 mg/mL (184.2 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years