Photoswitchable ORG25543 Congener Enables Optical Control of Glycine Transporter 2

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Abstract

Glycine neurotransmission in the dorsal horn of the spinal cord plays a key role in regulating nociceptive signaling, but in chronic pain states reduced glycine neurotransmission is associated with the development of allodynia and hypersensitivity to painful stimuli. This suggests that restoration of glycine neurotransmission may be therapeutic for the treatment of chronic pain. Glycine transporter 2 inhibitors have been demonstrated to enhance glycine neurotransmission and provide relief from allodynia in rodent models of chronic pain. In recent years, photoswitchable compounds have been developed to provide the possibility of controlling the activity of target proteins using light. In this study we have developed a photoswitchable noncompetitive inhibitor of glycine transporter 2 that has different affinities for the transporter at 365 nm compared to 470 nm light.

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Mostyn, S. N., Sarker, S., Muthuraman, P., Raja, A., Shimmon, S., Rawling, T., … Vandenberg, R. J. (2020). Photoswitchable ORG25543 Congener Enables Optical Control of Glycine Transporter 2. ACS Chemical Neuroscience, 11(9), 1250–1258. https://doi.org/10.1021/acschemneuro.9b00655

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