Virtual Screening of Small Drug-Like Compounds Stimulating the Enzymatic Activity of Kallikrein-Related Peptidase3 (KLK3)

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 therap...

Full description

Saved in:
Bibliographic Details
Published in:ChemMedChem 2016-09, Vol.11 (18), p.2043-2049
Main Authors: Ylikangas, Henna, Mattsson, Johanna M, Stenman, Ulf-Håkan, Koistinen, Hannu, Poso, Antti, Lahtela-Kakkonen, Maija
Format: Article
Language:English
Subjects:
Prostate cancer
Proteases
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.201600181