Back to Search
Start Over
Application of drug repositioning strategy to TOFISOPAM
- Source :
- Current Medicinal Chemistry, Current Medicinal Chemistry, Bentham Science Publishers, 2008, 15, pp.3196-3203
- Publication Year :
- 2008
-
Abstract
- Drug repositioning strategy is an interesting approach for pharmaceutical companies; especially to increase their productivity. SELNERGY(tm) 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.
- Subjects :
- Drug
Models, Molecular
media_common.quotation_subject
Drug Evaluation, Preclinical
Molecular Conformation
Pharmacology
Biochemistry
Benzodiazepines
Structure-Activity Relationship
Phosphodiesterase-4
Drug Discovery
medicine
Computer Simulation
PDE4 Inhibitors
ComputingMilieux_MISCELLANEOUS
Chromatography, High Pressure Liquid
media_common
Virtual screening
Chemistry
Organic Chemistry
Tofisopam
Stereoisomerism
Reverse docking
Cyclic Nucleotide Phosphodiesterases, Type 4
Drug repositioning
Models, Chemical
Molecular Medicine
Phosphodiesterase 4 Inhibitors
Biochemical mechanism
medicine.drug
Subjects
Details
- ISSN :
- 09298673
- Volume :
- 15
- Issue :
- 30
- Database :
- OpenAIRE
- Journal :
- Current medicinal chemistry
- Accession number :
- edsair.doi.dedup.....e2b11f6bdfb6c4dd397ca752c9f8b95e