Experimental confirmation of new drug-target interactions predicted by drug profile matching

László Végner, Ágnes Peragovics, László Tombor, Balázs Jelinek, Pál Czobor, Andreas Bender, Zoltán Simon, András Málnási-Csizmadia

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We recently introduced Drug Profile Matching (DPM), a novel affinity fingerprinting-based in silico drug repositioning approach. DPM is able to quantitatively predict the complete effect profiles of compounds via probability scores. In the present work, in order to investigate the predictive power of DPM, three effect categories, namely, angiotensin-converting enzyme inhibitor, cyclooxygenase inhibitor, and dopamine agent, were selected and predictions were verified by literature analysis as well as experimentally. A total of 72% of the newly predicted and tested dopaminergic compounds were confirmed by tests on D1 and D2 expressing cell cultures. 33% and 23% of the ACE and COX inhibitory predictions were confirmed by in vitro tests, respectively. Dose-dependent inhibition curves were measured for seven drugs, and their inhibitory constants (Ki) were determined. Our study overall demonstrates that DPM is an effective approach to reveal novel drug-target pairs that may result in repositioning these drugs.

Original languageEnglish
Pages (from-to)8377-8388
Number of pages12
JournalJournal of Medicinal Chemistry
Volume56
Issue number21
DOIs
Publication statusPublished - Nov 14 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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