YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo

2011 ◽  
Vol 102 (7) ◽  
pp. 1374-1380 ◽  
Author(s):  
Shu Tian ◽  
Haitian Quan ◽  
Chengying Xie ◽  
Haiyi Guo ◽  
Fangfang Lü ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Selective Inhibitor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Analysis of Plant-derived Phytochemicals as Anti-cancer Agents Targeting Cyclin Dependent Kinase-2, Human Topoisomerase IIa and Vascular Endothelial Growth Factor Receptor-2

2020 ◽  
Author(s):  
Bishajit Sarkar ◽  
Md. Asad Ullah ◽  
Syed Sajidul Islam ◽  
Md. Hasanur Rahman
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Cyclin Dependent Kinase ◽  
Molecular Docking Study ◽  
Topoisomerase Iiα ◽  
Endothelial Growth Factor

AbstractCancer is caused by a variety of pathways, involving numerous types of enzymes, among them three enzymes: Cyclin dependent kinase-2 (CDK-2), Human topoisomerase IIα and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three most common enzymes that are involved in the cancer development. Although many chemical drugs are available in the market, plant sources are known to contain a wide variety of agents that are known to possess anticancer activity. In this experiment, total thirty compounds were analysed against the mentioned enzymes using different tools of bioinformatics and in silico biology like molecular docking study, druglikeness property experiment, ADME/T test, PASS prediction and P450 site of metabolism prediction as well as DFT calculations to determine three best ligands that have the capability to inhibit the mentioned enzymes. Form the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed best inhibitory activities towards Human topoisomerase IIα and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analysis are required to confirm their safety and efficacy in this regard.

scholarly journals Anti-cancer effects of F16: A novel vascular endothelial growth factor receptor–specific inhibitor

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831772684 ◽  
Author(s):  
Appu Rathinavelu ◽  
Khalid Alhazzani ◽  
Sivanesan Dhandayuthapani ◽  
Thanigaivelan Kanagasabai
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Growth ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Vascular Endothelial ◽  
And Migration ◽  
Endothelial Growth Factor

Vascular endothelial growth factor receptor-2 is a dynamic target for therapeutic intervention in various types of cancers. This study was aimed to explore the anti-angiogenic activity of a novel vascular endothelial growth factor receptor–specific inhibitor named F16 in both in vitro and in vivo experimental models. This compound effectively reduced cell proliferation, tube formation, and migration of human umbilical vein endothelial cells in a concentration-dependent manner by directly inhibiting vascular endothelial growth factor binding and subsequent vascular endothelial growth factor receptor-2 phosphorylation. The F16 was also able to inhibit the phosphoinositide 3-kinase/protein kinase B–mediated survival and migration pathways in cancer in addition to inhibiting the focal adhesion kinase and mitogen-activated protein kinases–mediated signaling in GI-101A cancer cells. The chorioallantoic membrane assay followed by tumor growth inhibition measurements with GI-101A breast cancer xenograft implanted athymic nude mice confirmed the in vivo tumor reductive effects of F16. It was interesting to observe a decrease in tumor burden after F16 treatment which correlated very well with the decrease in the plasma levels of mucin-1 (MUC-1). Our studies so far have confirmed that F16 is a specific inhibitor of angiogenesis in both in vitro and in vivo models. The F16 also works very efficiently with Taxol in combination by limiting the tumor growth that is better than the monotherapy with any one of the drugs that were tested individually. Thus, F16 offers a promising anti-proliferative and anti-angiogenic effects with better specificity than some of the existing multi-kinase inhibitors.

scholarly journals Design, synthesis, and antitumor activity of novel benzoheterocycle derivatives as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase

2020 ◽  
Vol 44 (5-6) ◽  
pp. 286-294
Author(s):  
Yangyang Ding ◽  
Kai Liu ◽  
Xinyu Zhao ◽  
Yingtao Lv ◽  
Rilei Yu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Tyrosine Kinase ◽  
Human Cancer ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.

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