Browsing by Author "Derksen, Darren J"

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    Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators
    (2016-01) LeGay, Christina M; Gorobets, Evgueni; Iftinca, Mircea; Ramachandran, Rithwik; Altier, Christophe; Derksen, Darren J
    A library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca(2+) assays and electrophysiology.
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    Pannexin 1 Channels as a Therapeutic Target: Structure, Inhibition, and Outlook
    (2020-01) Navis, Kathleen E; Fan, Churmy Y; Trang, Tuan; Thompson, Roger J; Derksen, Darren J
    Pannexin 1 (Panx1) channels are transmembrane proteins that release adenosine triphosphate and play an important role in intercellular communication. They are widely expressed in somatic and nervous system tissues, and their activity has been associated with many pathologies such as stroke, epilepsy, inflammation, and chronic pain. While there are a variety of small molecules known to inhibit Panx1, currently little is known about the mechanism of channel inhibition, and there is a dearth of sufficiently potent and selective drugs targeting Panx1. Herein we provide a review of the current literature on Panx1 structural biology and known pharmacological agents that will help provide a basis for rational development of Panx1 chemical modulators.