Cediranib maleate (AZD-2171 maleate)
(Synonyms: 西地尼布马来酸盐; AZD-2171 maleate) 目录号 : GC33004
An inhibitor of VEGF receptor tyrosine kinases
Cas No.:857036-77-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. | |
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-
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)
| 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 |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 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。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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.