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The Discovery of Compounds That Stimulate the Activity of Kallikrein‐Related Peptidase 3 (KLK3)
Author(s) -
Härkönen Henna H.,
Mattsson Johanna M.,
Määttä Juha A. E.,
Stenman UlfHåkan,
Koistinen Hannu,
Matero Sanni,
Windshügel Björn,
Poso Antti,
LahtelaKakkonen Maija
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100349
Subject(s) - pharmacophore , chemistry , kallikrein , prostate cancer , prostate specific antigen , in vivo , small molecule , biochemistry , computational biology , cancer , enzyme , biology , medicine , microbiology and biotechnology
Kallikrein‐related peptidase 3 (KLK3), also known as prostate‐specific antigen (PSA), is the most useful biomarker for prostate cancer (PCa). KLK3 is suggested to play a role in regulating cancer growth through anti‐angiogenic activity in vivo and in vitro. This feature, together with its specificity for prostate tissue, makes KLK3 an intriguing target for the design of new therapies for PCa. 3D pharmacophores for KLK3‐stimulating compounds were generated based on peptides that bind specifically to KLK3 and increase its enzymatic activity. As a result of pharmacophore‐based virtual screening, four small, drug‐like compounds with affinity for KLK3 were discovered and validated by capillary differential scanning calorimetry. One of the compounds also stimulated the activity of KLK3, and is therefore the first published small molecule with such an activity.