Virtual Screening of Small Drug‐Like Compounds Stimulating the Enzymatic Activity of Kallikrein‐Related Peptidase 3 (KLK3) |
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| Authors: | Henna Ylikangas Dr Johanna M Mattsson Prof Ulf‐Håkan Stenman Dr Hannu Koistinen Prof Antti Poso Dr Maija Lahtela‐Kakkonen |
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| Affiliation: | 1. School of Pharmacy, University of Eastern Finland, Kuopio, Finland;2. Department of Clinical Chemistry, Biomedicum Helsinki, University ofHelsinki and, Helsinki University Central Hospital, Helsinki, Finland;3. University Hospital Tübingen, Department of Internal Medicine 1, Division of Molecular Oncology of Solid Tumors, Tübingen, Germany |
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| Abstract: | 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. |
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| Keywords: | angiogenesis cancer kallikrein molecular modeling virtual screening |
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