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Inhibitors of Cathepsins K and S Identified Using the DynaMAD Virtual Screening Algorithm
Author(s) -
Stumpfe Dagmar,
Sisay Mihiret T.,
Frizler Maxim,
Vogt Ingo,
Gütschow Michael,
Bajorath Jürgen
Publication year - 2010
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.200900457
Subject(s) - electrophile , cathepsin , cathepsin l , cysteine , cathepsin k , chemistry , virtual screening , computer science , covalent bond , computational biology , combinatorial chemistry , cathepsin b , algorithm , small molecule , biochemistry , stereochemistry , information retrieval , drug discovery , biology , enzyme , catalysis , organic chemistry , in vitro , osteoclast
A mapping algorithm that operates in high‐dimensional chemical reference spaces was applied to search for cathepsin K and S inhibitors. So far only a few cathepsin inhibitors lack a strong electrophilic group, which in most cases binds covalently to the catalytic cysteine. By testing only 10 of ∼3.7×10 6 source compounds, we identified two with micromolar potency and scaffolds distinct from known cathepsin inhibitors that inhibit both cathepsins K and S, but not L; both molecules lack a reactive electrophilic group.
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