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Cryo-EM structure of small-molecule agonist bound delta opioid receptor-Gi complex enables discovery of biased compound

Autor: Lin Cheng, Zhuang Miao, Sicen Liu, Zhe Li, Hong Fu, Chanjuan Xu, Shilong Hu, Chang Zhao, Yuxuan Liu, Tiantian Zhao, Wencheng Liu, Heli Wang, Runduo Liu, Wei Yan, Xiangdong Tang, Jianfeng Liu, Zhenhua Shao, Bowen Ke

Publikováno v: Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)

Abstract Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its poten

Externí odkaz: https://doaj.org/article/cb33bcfa1c674c8684c73a0815c0c282

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A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in mouse models of tumor-associated and provoked seizures.

Autor: Rifkin RA; Department of Neurology, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: rr3302@cumc.columbia.edu., Wu X; Department of Neurological Surgery, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: xw2013@cumc.columbia.edu., Pereira B; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, Mailbox 23, New York, NY, 10032, USA. Electronic address: bp2401@cumc.columbia.edu., Gill BJ; Department of Neurological Surgery, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: bjg2140@cumc.columbia.edu., Merricks EM; Department of Neurology, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: em3217@cumc.columbia.edu., Michalak AJ; Department of Neurology, New York University Grossman School of Medicine, 222 East 41st Street, 14th Floor New York, NY, 10017, USA. Electronic address: andrew.michalak@nyulangone.org., Goldberg AR; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, Mailbox 23, New York, NY, 10032, USA. Electronic address: ag3311@cumc.columbia.edu., Humala N; Department of Neurological Surgery, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: nh2560@cumc.columbia.edu., Dovas A; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, Mailbox 23, New York, NY, 10032, USA. Electronic address: ad3106@cumc.columbia.edu., Rai G; National Center for Advancing Translational Sciences, National Institutes of Health, 9609 Medical Center Drive, Rockville, MD, 20850-9793, USA. Electronic address: bantukallug@mail.nih.gov., McKhann GM; Department of Neurological Surgery, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: gm317@cumc.columbia.edu., Slesinger PA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029-5674, USA. Electronic address: Paul.Slesinger@mssm.edu., Canoll P; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, Mailbox 23, New York, NY, 10032, USA. Electronic address: pc561@cumc.columbia.edu., Schevon C; Department of Neurology, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address: cas2044@cumc.columbia.edu.

Publikováno v: Neuropharmacology [Neuropharmacology] 2024 Dec 09; Vol. 265, pp. 110259. Date of Electronic Publication: 2024 Dec 09.