Application of Drug Repositioning Strategy to TOFISOPAM

被引：17

作者：

Bernard, P. ^{[1
]}

Dufresne-Favetta, C. ^{[2
]}

Favetta, P. ^{[2
]}

Do, Q. -T. ^{[1
]}

Himbert, F. ^{[1
]}

Zubrzycki, S. ^{[2
]}

Scior, T. ^{[1
]}

Lugnier, C. ^{[3
]}

机构：

[1] GREENPHARMA SA, F-45100 Orleans, France

[2] Univ Orleans, CNRS, UMR 6005, ICOA, F-45067 Orleans, France

[3] CNRS, UMR 7175, F-67401 Illkirch Graffenstaden, France

来源：

CURRENT MEDICINAL CHEMISTRY | 2008年 / 15卷 / 30期

关键词：

Reverse docking; PDE4; SELNERGY; chiral purification;

D O I：

10.2174/092986708786848488

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3196 / 3203

页数：8

共 16 条

[1]

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[2]

Bourguignon J.-J., 2002, WO Patent, Patent No. [02/088096, 02088096]

[3]

Carley DW, 2005, IDRUGS, V8, P310

[4]

Carley DW, 2005, IDRUGS, V8, P306