N-[2-氯-4-[(6,7-二甲氧基-4-喹啉基)氧基]苯基]-N'-(5-甲基-3-异恶唑基)脲

• 常用名: N-[2-氯-4-[(6,7-二甲氧基-4-喹啉基)氧基]苯基]-N'-(5-甲基-3-异恶唑基)脲
• 英文名: Tivozanib
• CAS号: 682745-41-1
• 分子量: 509.33900
• 密度: N/A
• 沸点: N/A
• 分子式: C₂₂H₂₂Cl₂N₄O₆
• 熔点: N/A
• 闪点: N/A

用途

Tivozanib hydrochloride hydrate is a potent and selective and orally active VEGFR tyrosine kinase inhibitor with IC50是of 0.21, 0.16, 0.24 nM for VEGFR-1, VEGFR-2, VEGFR-3, respectively. Tivozanib hydrochloride hydrate inhibits angiogenesis and vascular permeability in tumor tissues and shows antitumor activity. Tivozanib hydrochloride hydrate has the potential for the research of metastatic renal cell carcinoma (RCC) [1][2][3].

名称

• 中文名: N-[2-氯-4-[(6,7-二甲氧基-4-喹啉基)氧基]苯基]-N'-(5-甲基-3-异恶唑基)脲
• 英文名: 1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea,hydrate,hydrochloride

生物活性

• 描述: 盐酸替沃扎尼水合物是一种有效、选择性和口服活性VEGFR酪氨酸激酶抑制剂,具有IC50是分别为0.21、0.16、0.24 nM。盐酸替沃扎尼水合物抑制肿瘤组织中的血管生成和血管通透性,并显示出抗肿瘤活性。盐酸替沃扎尼水合物具有研究转移性肾细胞癌的潜力[1][2][3]。
• 相关类别:
  研究领域 >> 癌症
  信号通路 >> 蛋白酪氨酸激酶 >> VEGFR
• 靶点:

  VEGFR-1:0.21 nM (IC50)

  VEGFR-2:0.16 nM (IC50)

  VEGFR-3:0.24 nM (IC50)

• 体外研究: 盐酸替沃扎尼水合物抑制VEGFR-1、VEGFR-2和VEGFR-3的磷酸化[2]。
• 体内研究: 盐酸替沃扎尼水合物(1 mg/kg；p.o.；14天)抑制CNV病变的发展,并导致已建立的CNV显著消退,使受影响区域减少67.7%[4]。
• 参考文献:

  [1]. Motzer RJ, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013 Oct 20;31(30):3791-9.

  [2]. De Luca A, et al. Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the potential treatment of solid tumors. IDrugs. 2010 Sep;13(9):636-45.

  [3]. Eskens FA, det al. Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors. Clin Cancer Res. 2011 Nov 15;17(22):7156-63.

  [4]. Kang S, et al. Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization in mice. Exp Eye Res. 2013 Jul;112:125-33.

物理化学性质

• 分子式: C₂₂H₂₂Cl₂N₄O₆
• 分子量: 509.33900
• 精确质量: 508.09200
• PSA: 123.69000
• LogP: 5.81130
• 储存条件: -20°C

英文别名

• Tivozanib hydrochloride monohydrate
• UNII-8A9H4VK35Z
• Tivozanib hydrochloride hydrate
• Tivozanib HCl hydrate
• Kil-8951
• Tivozanib HCl