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Cediranib maleate (AZD-2171 maleate) Sale

(Synonyms: 西地尼布马来酸盐; AZD-2171 maleate) 目录号 : GC33004

An inhibitor of VEGF receptor tyrosine kinases

Cediranib maleate (AZD-2171 maleate) Chemical Structure

Cas No.:857036-77-2

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥561.00
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5mg
¥450.00
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10mg
¥675.00
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50mg
¥2,160.00
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100mg
¥3,420.00
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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实验参考方法

Kinase experiment:

The inhibitory activity of Cediranib is determined against a range of recombinant tyrosine kinases [KDR, Flt-1, Flt-4, c-Kit, PDGFR-α, PDGFR-β, CSF-1R, Flt-3, FGFR1, Src, Abl, epidermal growth factor receptor (EGFR), ErbB2, Aur-A, and Aur-B] using ELISA methodology[1].

Cell experiment:

Proliferation of MG63 osteosarcoma cells is induced by PDGF-AA, which selectively activates PDGFR-α homodimer signaling. 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 reincubated for 72 hours. Cellular proliferation is determined using a bromodeoxyuridine[1].

Animal experiment:

Rats: Young female Alderley Park rats (6 weeks of age, Wistar derived, n=5) are dosed orally, once daily for 28 days with Cediranib (1.25-5 mg per kg per day) or vehicle. Additional rats (five per group) are treated with Cediranib (5 mg per kg per day) or vehicle for 28 days and maintained for a further 28 days without treatment, to examine the effect of compound withdrawal. Histologic paraffin wax sections of the femorotibial joints and ovaries are stained with H&E. Morphometric image analysis of femorotibial sections is done, with growth plate areas from both the femur and tibia in each joint being combined for an analysis of the effect of compound treatment. The area of corpora lutea in H&E-stained ovary sections is similarly determined by morphometric analysis[1].

References:

[1]. Wedge SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res, 2005, 65(10), 4389-4400.

产品描述

Receptors for VEGF have central roles in vasculogenesis and angiogenesis and thus serve as targets for cancer therapy.1,2 Cediranib is a potent inhibitor of VEGF receptor tyrosine kinases, including VEGFR1, 2, and 3 (IC50s = 5, 1, and 3 nM, respectively).3 It also potently inhibits a variety of other receptor and non-receptor tyrosine kinases, including several in the platelet-derived growth factor, fibroblast growth factor, and endothelial growth factor receptor families.3,4 Cediranib blocks tubule formation by human umbilical vein endothelial cells in vitro and prevents angiogenesis as well as xenograft tumor growth in vivo.3 Because of these effects, cediranib has potential use in a range of cancers.5,6,7

1.Rini, B.I.Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinomaCancer115(10 Suppl)2306-2312(2009) 2.Burger, R.A.Overview of anti-angiogenic agents in development for ovarian cancerGynecol. Oncol.121(1)230-238(2011) 3.Wedge, S.R., Kendrew, J., Hennequin, L.F., et al.AZD2171: A highly potent, orally bioavailable vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancerCancer Res.65(10)4389-4400(2005) 4.Davis, M.I., Hunt, J.P., Herrgard, S., et al.Comprehensive analysis of kinase inhibitor selectivityNat. Biotechnol.29(11)1046-1051(2011) 5.Bhargava, P., and Robinson, M.O.Development of second-generation VEGFR tyrosine kinase inhibitors: Current statusCurr. Oncol. Rep.13(2)103-111(2011) 6.Conti, A., Santoni, M., Amantini, C., et al.Progress of molecular targeted therapies for advanced renal cell carcinomaBiomed Res. Int.2013419176(2013) 7.Castelli, C., Tazzari, M., Negri, T., et al.Structured myeloid cells and anti-angiogenic therapy in alveolar soft part sarcomaJ. Transl. Med.11(1)237(2013)

Chemical Properties

Cas No. 857036-77-2 SDF
别名 西地尼布马来酸盐; AZD-2171 maleate
Canonical SMILES O=C(O)/C=C\C(O)=O.FC1=C(OC2=C(C(C=C3OCCCN4CCCC4)=NC=N2)C=C3OC)C=CC5=C1C=C(C)N5
分子式 C29H31FN4O7 分子量 566.58
溶解度 DMSO : ≥ 45 mg/mL (79.42 mM);Water : 2 mg/mL (3.53 mM) 储存条件 Store at -20°C
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 1.765 mL 8.8249 mL 17.6498 mL
5 mM 0.353 mL 1.765 mL 3.53 mL
10 mM 0.1765 mL 0.8825 mL 1.765 mL
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Research Update

Cediranib Maleate-From Crystal Structure Toward Materials Control

J Pharm Sci 2020 Apr;109(4):1509-1518.PMID:31884015DOI:10.1016/j.xphs.2019.12.017.

Cediranib maleate is an active pharmaceutical ingredient (API) in phase III of development within AstraZeneca's oncology portfolio. Analysis of the crystal structure of this API confirmed that the selected salt form was robust. The salt formation step had to be redesigned to avoid an unwanted metastable polymorph. A solvate with a twist appeared during later development and was avoided using insights gained from its crystal structure. Differences between predicted and experimental aspect ratios correlate with weaker crystal interactions. Acceptable variability in particle size was defined and accommodated. The "Matwall" is introduced as a tool for building control of API performance from the crystal structure upward.

Topical noninvasive retinal drug delivery of a tyrosine kinase inhibitor: 3% Cediranib maleate cyclodextrin nanoparticle eye drops in the rabbit eye

Acta Ophthalmol 2022 Nov;100(7):788-796.PMID:35080812DOI:10.1111/aos.15101.

Purpose: Tyrosine kinase inhibitors inhibit VEGF receptors. If delivered to the retina, they might inhibit oedema and neovascularization such as in age-related macular degeneration and diabetic retinopathy. The aim of this study was to formulate Cediranib maleate, a potent VEGF inhibitor, as γ-cyclodextrin nanoparticle eye drops and measure the retinal delivery and overall ocular pharmacokinetics after a single-dose administration in rabbits. Methods: A novel formulation technology with 3% Cediranib maleate as γ-cyclodextrin micro-suspension was prepared by autoclaving method. Suitable stabilizers were tested for heat-stable eye drops. The ophthalmic formulation was topically applied to one eye in rabbits. The pharmacokinetics in ocular tissues, tear film and blood samples were studied at 1, 3 and 6 hr after administration. Results: γ-cyclodextrin formed complex with Cediranib maleate. The formation of γ-cyclodextrin nanoparticles occurred in concentrated complexing media. Combined stabilizers prevented the degradation of drug during the autoclaving process. Three hours after administration of the eye drops, treated eyes showed cediranib levels of 737 ± 460 nM (mean ± SD) in the retina and 10 ± 6 nM in the vitreous humour. Conclusions: Cediranib maleate in γ-cyclodextrin nanoparticles were stable to heat in presence of stabilizers. The drug as eye drops reached the retina in concentrations that are more than 100 times higher than the 0.4 nM IC50 value reported for the VEGF type-II receptor and thus, presumably, above therapeutic level. These results suggest that γ-cyclodextrin-based Cediranib maleate eye drops deliver effective drug concentrations to the retina in rabbits after a single-dose administration.