An In-silico Study of Pathological Angiogenesis; Design of Anticancer Agent Inhibiting KLK – 12

A critical route for cancer metastases is pathological angiogenesis. A functional role in angiogenesis has been reported for the serine protease protein Kallikrein-12 (KLK-12). Cysteine-rich angiogenic inducer 61 (CYR61) protein is hydrolyzed by the KLK-12 protein, which also regulates the bioavailability of growth factors that induce angiogenesis. The chapter discusses the homology modeling of the KLK-12 protein, identify essential residues to be putatively linked to the natural substrate. Protein-Protein docking is done to characterize Trp35, Gln36, Gly38, Trp82 and His107 residues of the active site. Using Auto Dock Vina software, virtual screening studies were carried out to identify the substituted carboxamide scaffolds as a pharmacophore binding at the active site. Based on binding energy, ADME, and visual inspection, an isochromene carboxamide moiety is identified as antiangiogenic and cancer antagonists. The isochromene carboxamide scaffold has a stronger interaction behave as potent antiangiogenic ligand against KLK-12 in cancer.