angiogenesis

Pathological angiogenesis is a critical pathway for cancer metastases. The protein Kallikrein-12 (KLK-12) has been reported to play a functional role in angiogenesis. It hydrolyzes the CYR61 protein, a cysteine-rich angiogenic inducer, and also regulates the availability of growth factors that induce angiogenesis. This chapter focuses on the homology modeling of the KLK-12 protein and identifies essential residues that are potentially linked to the natural substrate. Protein-protein docking is used to characterize the active site residues, including Trp35, Gln36, Gly38, Trp82, and His107. The Auto Dock Vina software is used to carry out virtual screening studies to identify substituted carboxamide scaffolds that can bind to the active site as a pharmacophore. Based on binding energy, ADME, and visual inspection, an isochromene carboxamide moiety is identified as an anti-angiogenic and cancer antagonist. The isochromene carboxamide scaffold has a potent interaction and behaves as a strong antiangiogenic ligand against KLK-12 in cancer.

Author(s) Details:

Jyothi Bandi,
Department of Chemistry, University College of Science, Osmania University, Hyderabad – 500007, Telangana State, India.

Navaneetha Nambigari,
Department of Chemistry, University College of Science, Osmania University, Hyderabad – 500007, Telangana State, India and Department of Chemistry, University College of Science, Saifabad, Osmania University, Hyderabad – 500004, Telangana State, India.

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