Identification of Novel Anticancer Agent by in silico Methods for Inhibition of KLK-12 Protein

Abstract

A critical route for cancer metastases is pathological angiogenesis. The protein Kallikrein-12 (KLK-12) is a serine protease reported to be involved in a variety of biochemical processes that have a functional role in angiogenesis. The KLK-12 protein hydrolyzes the cysteine rich angiogenic inducer 61 (CYR61) protein and controls the bioavailability of angiogenesis-inducing growth factors. The work proposed involves 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, in addition to active site servers (active site prediction server and CASTp). 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.