Virtual Screening of Small Drug-Like Compounds Stimulating the Enzymatic Activity of Kallikrein-Related Peptidase 3 (KLK3)
| Autor: | Hannu Koistinen, Johanna M. Mattsson, Ulf-Håkan Stenman, Henna Ylikangas, Maija Lahtela-Kakkonen, Antti Poso |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Evaluation Preclinical Biochemistry Small Molecule Libraries 03 medical and health sciences Prostate cancer Structure-Activity Relationship 0302 clinical medicine Drug Discovery medicine Humans Protease Inhibitors General Pharmacology Toxicology and Pharmaceutics Pharmacology chemistry.chemical_classification Serine protease Virtual screening biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Kallikrein Prostate-Specific Antigen medicine.disease Molecular biology Cyclic peptide Enzyme Activation Prostate-specific antigen 030104 developmental biology Enzyme 030220 oncology & carcinogenesis biology.protein Molecular Medicine Kallikreins Pharmacophore |
| Zdroj: | ChemMedChem. 11(18) |
| ISSN: | 1860-7187 |
| Popis: | Kallikrein-related peptidase 3 (KLK3) is a prostatic serine protease shown to possess antiangiogenic properties which are exerted via its proteolytic activity. The antiangiogenic effect indicates that KLK3 may slow down the growth of prostate cancer; this makes it an interesting target for new therapies for prostate cancer. In this work, new drug-like compounds were discovered that stimulate the proteolytic activity of KLK3. The compounds were identified using 2D similarity search and 3D pharmacophore-based virtual screening, and their ability to stimulate KLK3 was verified by enzymatic activity assays. The effect of the molecules alone was modest, but in synergy with a cyclic peptide the most potent molecule was found to stimulate KLK3 activity significantly: up to 351 % of the activity of KLK3. This demonstrates that small drug-like compounds can be beneficial tools in studying the antiangiogenic properties of KLK3. |
| Databáze: | OpenAIRE |
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