Browsing by Author "Navis, Kathleen E."

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    Design, Synthesis and Evaluation of Novel Pannexin 1 Channel Modulators
    (2020-10-26) Navis, Kathleen E.; Derksen, Darren J.; Sutherland, Todd C.; MacCallum, Justin L.; Van Humbeck, Jeffrey F.
    Pannexin 1 (Panx1) channels are transmembrane proteins that release ATP 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 including stroke, epilepsy, addiction, inflammation and chronic pain. While there are a variety of known Panx1 inhibitors, there is a dearth of sufficiently potent and selective drugs targeting Panx1, and relatively little is known about the mechanism of channel inhibition. Structure-activity relationship (SAR) studies can provide information about the critical functional groups controlling substrate activity and lead to the development of more potent inhibitors. This thesis outlines the importance of Panx1 channels as a potential therapeutic target and describes the synthesis, SAR and evaluation of novel inhibitors based on biological assays. In silico modeling was also used to identify compounds from the ZINC database with similar pharmacophore characteristics to known Panx1 inhibitors. The compounds developed over the course of study may have potential as novel drugs for the relief of multiple important pathologies. Provisional patent protection for this work is currently being pursued.