CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.
CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.
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CPU-12 是一种新型合成的恶唑并[5,4-d]嘧啶衍生物，具有优异的抗血管生成活性。
DOI：
10.1016/j.jphs.2015.06.001
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发表时间：
2015
影响因子：
3.5
通讯作者：
Yu Liu
中科院分区：
文献类型：
--
作者：
Ji;Ya‐Hui Deng;Ling Yang;Yijuan Chen;M. Lawali;Li‐Ping Sun;Yu Liu
血管生成是恶性肿瘤生长、进展和转移的关键条件。肿瘤衍生因子刺激新血管的形成，这些新血管积极支持肿瘤生长和扩散。各种药物已被应用于抑制肿瘤血管生成。CPU-12，4-氯-N-（4-（（2-（4-甲氧基苯基）-5-甲基恶唑并[5，4-d]嘧啶-7-基）氨基）苯基）苯甲酰胺，是一种新型恶唑并[5，4-d]嘧啶衍生物，在体外和离体实验中显示出有效的抑制VEGF诱导的血管生成的活性。在细胞毒性实验中，CPU-12以剂量依赖方式显著抑制人脐静脉内皮细胞（HUVEC）增殖，IC 50值较低，为9.30 ± 1.24 μM。在体外实验中，CPU-12能显著抑制HUVEC的迁移、趋化侵袭和毛细血管样管的形成，并呈剂量依赖性。在体外，CPU-12有效地抑制新的微血管发芽从大鼠主动脉环。此外，CPU-1/2还能有效下调血管内皮生长因子受体-2（VEGFR-2）的下游信号通路，包括PI 3 K、ERK 1/2和p38 MAPK的磷酸化。这些证据表明，通过不同的信号转导途径调节内皮细胞的增殖，迁移和管形成的诱导VEGFR的血管生成反应在体外和离体显着抑制由新的小分子化合物CPU-12。总之，CPU-12在体外显示出上级的抗血管生成活性。
Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro.
影响因子：
3.8
作者：
Wang, K.;Jiang, Y-z.;Chen, D-b.;Zheng, J.
通讯作者：
Zheng, J.