title: New directions for protease inhibitors directed drug discovery.
abstract: Proteases play crucial roles in various biological processes, and their activities are essential for all living organisms-from viruses to humans. Since their functions are closely associated with many pathogenic mechanisms, their inhibitors or activators are important molecular targets for developing treatments for various diseases. Here, we describe drugs/drug candidates that target proteases, such as malarial plasmepsins, β-secretase, virus proteases, and dipeptidyl peptidase-4. Previously, we reported inhibitors of aspartic proteases, such as renin, human immunodeficiency virus type 1 protease, human T-lymphotropic virus type I protease, plasmepsins, and β-secretase, as drug candidates for hypertension, adult T-cell leukaemia, human T-lymphotropic virus type I-associated myelopathy, malaria, and Alzheimer's disease. Our inhibitors are also described in this review article as examples of drugs that target proteases. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 563-579, 2016.
authors.affiliation: Medicinal Chemistry Laboratory, Kobe Pharmaceutical University, Motoyamakita, Higashinada-ku, Kobe, 658-8558, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Laboratory of Peptide Science, Nagahama Institute of Bio-Science and Technology, Tamura-cho, Nagahama, 526-0829, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D010447:Peptide Hydrolases / Q000737:chemistry*; D010961:Plasmodium / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D014780:Viruses / Q000201:enzymology*
chemical_list: D011480:Protease Inhibitors; D015800:Protozoan Proteins; D014764:Viral Proteins; D010447:Peptide Hydrolases
keywords: DPP-4; HCV NS3 protease; HIV-1 protease; plasmepsin; protease inhibitor; β-secretase