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J Med Chem. 2013 Nov 14;56(21):8377-88. doi: 10.1021/jm400813y. Epub 2013 Oct 23.

Experimental confirmation of new drug-target interactions predicted by Drug Profile Matching.

Author information

1
Department of Biochemistry, Institute of Biology, Eötvös Loránd University , Pázmány Péter sétány 1/C, H-1117 Budapest, Hungary.

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.

PMID:
24088053
DOI:
10.1021/jm400813y
[Indexed for MEDLINE]

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