Abstract
Drug repositioning strategy is an interesting approach for pharmaceutical companies ; especially to increase their productivity. SELNERGYtm is a reverse docking based-program able to virtually screen thousands of compounds on more than 2000 3D biological targets. This program was successfully applied to tofisopam and revealed that the isomers of tofisopam are able to fit with phosphodiesterase 4. This old drug was used as a racemic mixture to treat anxiety in the eighties and was recently shown to act as a PDE4 inhibitor. Thanks to this strategy we demonstrated that tofisopam acts via the inhibition of PDE4 in the submicromolar range. Moreover, we firstly showed that the S-enantiomer of tofisopam is ten times more active than R-enantiomer. The identification of the biochemical mechanism of tofisopam isomers now allows to reposition this drug in new therapeutic indications where modulation of cAMP via PDE4 inhibitors are possible.
Keywords: Reverse docking, PDE4, SELNERGY, chiral purification
Current Medicinal Chemistry
Title: Application of Drug Repositioning Strategy to TOFISOPAM
Volume: 15 Issue: 30
Author(s): P. Bernard, C. Dufresne-Favetta, P. Favetta, Q.-T. Do, F. Himbert, S. Zubrzycki, T. Scior and C. Lugnier
Affiliation:
Keywords: Reverse docking, PDE4, SELNERGY, chiral purification
Abstract: Drug repositioning strategy is an interesting approach for pharmaceutical companies ; especially to increase their productivity. SELNERGYtm is a reverse docking based-program able to virtually screen thousands of compounds on more than 2000 3D biological targets. This program was successfully applied to tofisopam and revealed that the isomers of tofisopam are able to fit with phosphodiesterase 4. This old drug was used as a racemic mixture to treat anxiety in the eighties and was recently shown to act as a PDE4 inhibitor. Thanks to this strategy we demonstrated that tofisopam acts via the inhibition of PDE4 in the submicromolar range. Moreover, we firstly showed that the S-enantiomer of tofisopam is ten times more active than R-enantiomer. The identification of the biochemical mechanism of tofisopam isomers now allows to reposition this drug in new therapeutic indications where modulation of cAMP via PDE4 inhibitors are possible.
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Cite this article as:
Bernard P., Dufresne-Favetta C., Favetta P., Do Q.-T., Himbert F., Zubrzycki S., Scior T. and Lugnier C., Application of Drug Repositioning Strategy to TOFISOPAM, Current Medicinal Chemistry 2008; 15 (30) . https://dx.doi.org/10.2174/092986708786848488
DOI https://dx.doi.org/10.2174/092986708786848488 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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