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Master Thesis

Investigation de la relation structure activité de l'acide flufénamique et de ses dérivés en tant qu'activateurs du canal TRESK humain

Abstract : TRESK (Twik Related Spinal cord K+ channel) is a member of the Twin Pore Domain K+ channel (K2P) family responsible for regulating neuronal excitability in dorsal root ganglion (DRG) and Trigeminal Neurons (TG), peripheral neurons involved in pain transmission. As channel opening causes an outward K+ current responsible for cell hyperpolarisation, TRESK represents a new interesting target for pain treatment. However, as no crystal structure exists for this K2P, the mechanisms involved in the opening effect of some ligands are still poorly understood, making the conception of new potent selective openers challenging. In this work we propose a Structure Activity Relationship (SAR) of the known TRESK opener Flufenamic acid (FFA) and some derivatives, investigating the biological effects of chemical modifications and using a human-TRESK (hTRESK) homology model to support the biological results. A plausible binding mode resulted from this study for the tested openers, providing the first predictive view of a hTRESK opener binding site.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-00929833
Contributor : Jean-Hugues Morneau <>
Submitted on : Tuesday, January 14, 2014 - 9:05:51 AM
Last modification on : Tuesday, May 11, 2021 - 11:36:16 AM
Long-term archiving on: : Saturday, April 8, 2017 - 3:09:20 PM

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  • HAL Id : dumas-00929833, version 1

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Aymeric Monteillier. Investigation de la relation structure activité de l'acide flufénamique et de ses dérivés en tant qu'activateurs du canal TRESK humain. Sciences pharmaceutiques. 2014. ⟨dumas-00929833⟩

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