Ligand-Based Virtual Screening to Identify New T-Type Calcium Channel Blockers

Ismail Ijjaali, Christian Barrere, Joel Nargeot, Francois Petitet and Emmanuel Bourinet

volume 1 | issue 4

July/August
Pages: 300 - 304

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T-type calcium channels are involved in the generation of rhythmical firing patterns in the mammalian central nervous system and in various pathological alterations of neuronal excitability such as in epilepsy or neuropathic pain. In the search for new T-type calcium channel blockers that would help to treat these disorders, we have followed a bi-dimensional pharmacophore-based virtual screening approach to identify new inhibitors. Nineteen molecules extracted from AurSCOPE Ion Channels knowledgebase were used as query molecules to screen an external database. This in silico approach was then validated using electrophysiology. Interestingly, 16 compounds out of 38 distinct molecules tested showed more than 50% blockade of the CaV3.2 mediated T-type current. Two series of compounds show chemical originality compared with known T-type calcium channel blockers.

Authors

Ismail Ijjaali

Aureus Pharma

Christian Barrere

Institut de Génomique Fonctionnelle

Joel Nargeot

Institut de Génomique Fonctionnelle

Francois Petitet

Aureus Pharma

Emmanuel Bourinet

Institut de Gn006fmique Fonctionnelle

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: