{'fraction_non_alphanumeric': 0.025711159737417943, 'fraction_numerical': 0.019146608315098467, 'mean_word_length': 5.328719723183391, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Discovery of Vascular Endothelial Growth Factor Receptor‐2 (VEGFR‐2) Inhibitors by Ligand‐based Virtual High Throughput Screening

In recent years, the inhibition of angiogenesis has become a target for anti‐cancer therapeutics. Angiogenesis' role in the cancerous cells is different from that when it is employed in the physiological homeostasis of cells. As the interest of angiogenesis inhibition has grown so has, the interest in the vascular endothelial growth factor receptor‐2 (VEGFR‐2) complex that is highly expressed in many cancers such as breast, kidney. The present study reports the successful application of ligand‐based virtual high throughput screening method for the discovery of novel VEGFR‐2 inhibitors. We generated a ligand query model with pharmacophore features from the reported VEGFR‐2 inhibitors using vROCS tool and performed virtual high throughput screening. Among the 2.4 million lead like molecules of ZINC database screened, nineteen prioritized compounds were purchased from Enamine and Chembridge screening libraries and tested for VEGFR‐2 inhibitory activity using Promega's ADP‐Glo™ kinase assay. Experimental validation led to the discovery of four compounds 3, 7, 10, and 13. Staurosporine, a known kinase inhibitor was used a standard for this assay. At the beginning, all the 19 compounds were tested for VEGFR2 inhibitory activity at 50μM. The results are displayed in figure 1. The compounds 3, 7, 10, and 13 showed more than 50% inhibition are shown in red bars. These compounds were then tested for their inhibitory activity at 10 μM. Figure 2 represents the VEGFR inhibitory activity for the selected compounds at 10 μM. Docking was performed for these compounds and the predicted binding modes guide to explore the possible structural changes to get more potent VEGFR‐2 inhibitors.