Cabozantinib (XL184,BMS-907351) 是一種新型 MET 和 VEGFR2 抑制劑，可同時(shí)抑制轉移、血管生成和腫瘤生長(cháng)[1]。其對 VEGFR2 和 c-Met 的 IC50 值分別為 0.035 nM 和 1.3 nM[2]。

Cabozantinib(XL184) 處理 MDA-MB-231 和 HCC70 細胞的 MAME 培養物（表達 HGF 的成纖維細胞）具有細胞毒性并顯著(zhù)減少多細胞侵襲性生長(cháng)，即使在含有表達 HGF 的成纖維細胞的培養物中也是如此[3]。 Cabozantinib 誘導的細胞應激導致 DU-145 細胞系發(fā)生 ICD（一種特殊類(lèi)型的細胞凋亡）[4]。據報道，卡博替尼可通過(guò)阻斷膀胱癌細胞中的 HGF-MET 信號通路來(lái)抑制 MMP-1 的表達[5]?？ú┨婺崽幚砗驟SCC細胞MMP-1顯著(zhù)降低，這是卡博替尼處理后ESCC細胞遷移活性降低的原因[6]。

卡博替尼抑制腫瘤生長(cháng)在嚙齒動(dòng)物的人類(lèi)腫瘤模型中呈劑量依賴(lài)性[1]。體內藥效學(xué)研究表明，單次口服卡博替尼[7]后，TT 異種移植腫瘤中的 RET 得到顯著(zhù)抑制。使用 CRC（結直腸癌）外植體模型，卡博替尼在體內表現出優(yōu)異的抗腫瘤作用[8]。

產(chǎn)品性質(zhì)：

Cas No.:849217-68-1

別名:卡博替尼; XL184; BMS-907351

化學(xué)名: 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Canonical SMILES COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F

分子式:C28H24FN3O5

分子量:501.51

溶解度:≥ 25.1mg/mL in DMSO

儲存條件:4°C, protect from light

注意事項：

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References:

[1]. Yakes F Michael,Chen Jason, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth.[J]. Molecular cancer therapeutics,2011,10(12).

[2]. Weon-Kyoo You, Barbara Sennino, et al. VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer[J]. Microenvironment and Immunology,2011.

[3]. Sameni Mansoureh,Tovar Elizabeth A, et al. Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models.[J]. Clinical cancer research : an official journal of the American Association for Cancer Research,2016,22(4).

[4] Scirocchi Fabio,Napoletano Chiara,et al. Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib[J]. Frontiers in Oncology,2021,11.

[5] Shintani T, Kusuhara Y, et al. The involvement of hepatocyte growth factor-MET-matrix metalloproteinase 1 signaling in bladder cancer invasiveness and proliferation. Effect of the MET inhibitor, cabozantinib (XL184), on bladder cancer cells. Urology. (2017) 101:169.e7-13. doi: 10.1016/j.urology.2016.12.006.

[6] Pei-Wen Yang, Yu-Cheng Liu, et al. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)[J]. Frontiers in Oncology, 2019.

[7] Bentzien Frauke,Zuzow Marcus, et al. In vitro and in vivo activity of cabozantinib (XL184), an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer.[J]. Thyroid : official journal of the American Thyroid Association,2013,23(12).

[8] Scott Aaron J,Arcaroli John J,et al. Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms.[J]. Molecular cancer therapeutics,2018,17(10).