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Axitinib

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Chemical Structure| 319460-85-0 同义名 : 阿西替尼 ;AG-013736
CAS号 : 319460-85-0
货号 : A226761
分子式 : C22H18N4OS
纯度 : 98%
分子量 : 386.469
MDL号 : MFCD09837898
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(51.75 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 1.5 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • VEGFR1

    VEGFR1/FLT1, IC50:0.1 nM

  • VEGFR3

    VEGFR3, IC50:0.1 nM-0.3 nM

  • VEGFR2

    VEGFR2/KDR, IC50:0.2 nM

    VEGFR2/Flk1, IC50:0.18 nM

  • PDGFRβ

    PDGFRβ, IC50:1.6 nM
描述 VEGF/VEGFR (vascular endothelial growth factor/vascular endothelial growth factor receptor) pathway plays a key role in tumor angiogenesis by promotion of vascular and lymphatic endothelial, as well as survival, and invasion, thus resulting in neovascularization, tumor growth and metastasis. Axitinib is a selective and potent VEGFR inhibitor with IC50 values of 0.1nM, 0.18nM, 0.2nM and 0.1nM-0.3nM for VEGFR1/FLT1, VEGFR2/Flk1, VEGFR2/KDR and VEGFR3, as well as less potent to PDGFRβ, Kit and PDGFRα with IC50 value of 1.6nM, 1.7nM and 5.0nM (measured by enzymatic assays), respectively. Treatment with Axitinib at concentration ranging in 1-300nM for 45min caused inhibition on downstream signaling induced by VEGF (50ng/ml), including p-AKT (>1nM), p-eNOS (>1nM) and p-ERK (>10nM), in a dose-dependent manner in HUVECs. Axitinib inhibited dose dependently VEGF-stimulated (20ng/ml) growth of HUVECs (for 3 days) with IC50 of 0.17nM, as well as blocked the sprouting and tube formation of human microvascular endothelial cell spheroids at 3, 6, 12.5, 25, and 50nM (for 7 days). Oral treatment with Axitinib at dose ranging in 3-150mg/kg showed dose-dependently tumor growth inhibition in MV522 tumor model, with reduced Ki-67 (marked cell division) and increased caspase-3 in the tumor. Axitinib also enhanced antitumor efficacy of chemotherapeutic agents, including docetaxel in LLC and human breast cancer models, carboplatin in a human ovarian cancer model and gemcitabine in a human pancreatic cancer model, as well as produced significant antimetastasis activity combined with bevacizumab in M24met model[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22RV1 Growth Inhibition Assay IC50=17.5884 μM SANGER
23132-87 Growth Inhibition Assay IC50=12.0821 μM SANGER
5637 Growth Inhibition Assay IC50=29.6421 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00692341 Hepatic Insufficiency Phase 1 Completed - United States, Florida ... 展开 >> Pfizer Investigational Site Miami, Florida, United States, 33169 Pfizer Investigational Site Orlando, Florida, United States, 32809 收起 <<
NCT03386929 Non-small Cell Lung Cancer Met... 展开 >>astatic Non-Small Cell Lung Cancer Stage IIIB 收起 << Phase 1 Phase 2 Recruiting December 2022 United States, California ... 展开 >> UCSD Moores Cancer Center Recruiting La Jolla, California, United States, 92093 Contact: Sarah MOORE       sam055@ucsd.edu    Principal Investigator: Lyudmila BAZHENOVA, MD          United States, South Dakota Avera Cancer Center Recruiting Sioux Falls, South Dakota, United States, 57105 Contact: Martha LANG       Martha.lang@avera.org    Principal Investigator: Benjamin SOLOMON, MD          France Centre Léon Bérard Recruiting Lyon, France, 69008 Contact: Séverine LAURENT       severine.laurent@lyon.unicancer.fr    Principal Investigator: Pierre SAINTIGNY, MD          Israel Chiam Sheba Medical Center Recruiting Ramat Gan, Israel, 5265601 Contact: Yona GILADY       yona.gilady@sheba.health.gov.il    Principal Investigator: Jair BAR, MD          Luxembourg Centre Hospitalier Luxembourg Recruiting Luxembourg, Luxembourg, 1210 Contact: Lucile PERNOT       lucile.pernot@lih.lu    Principal Investigator: Guy BERCHEM, MD          Spain Vall Hebron Institute of Oncology Recruiting Barcelona, Spain, 08035 Contact: LLuisa CARBONELL       llcarbonell@vhio.net    Principal Investigator: Enriqueta Felip, MD 收起 <<
NCT00389441 Thyroid Neoplasms Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.59mL

0.52mL

0.26mL

12.94mL

2.59mL

1.29mL

25.88mL

5.17mL

2.59mL
参考文献

[1]Hu-Lowe DD, Zou HY, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008;14(22):7272-83.

[2]Du Four S, Maenhout SK, et al. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. Oncoimmunology. 2015;4(4):e998107.

[3]Van der Veken B, De Meyer GRY, Martinet W. Axitinib attenuates intraplaque angiogenesis, haemorrhages and plaque destabilization in mice. Vascul Pharmacol. 2018.