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        TRPA1 in Drug Discovery

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        TRPA1 is one of the few ion channels with human genetic validation for pain. A TRPA1 gain-of-function mutation is linked to familial episodic pain syndrome in humans. This milestone discovery, coupled with a growing preclinical literature implicating TRPA1 in multiple indications, has made TRPA1 an attractive therapeutic target. With extensive investment across the pharmaceutical industry, several novel nonreactive TRPA1 antagonist series have emerged in patents, and two TRPA1 compounds have recently advanced to human clinical trials. A review of the diverse roles for TRPA1 in pain signaling and other indications such as itch and respiratory diseases is presented along with an overview of known small molecule activators and antagonists of the TRPA1 receptor.
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