期刊
CHEMMEDCHEM
卷 11, 期 18, 页码 2043-2049出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201600181
关键词
angiogenesis; cancer; kallikrein; molecular modeling; virtual screening
资金
- Finnish Pharmaceutical Society
- Magnus Ehrnrooth Foundation
- Finnish Concordia Foundation
- Finnish Pharmacists' Society
- Kuopio University Foundation
- Finnish Cancer Foundation
- Academy of Finland
- Sigrid Juselius Foundation
- Finska Lakaresallskapet
- Biomedicum Helsinki Foundation
- Faculty of Medicine, University of Helsinki
- Doctoral School of the University of Eastern Finland
- Doctoral Program in Drug Research
Kallikrein-related peptidase3 (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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