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PZM21

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https://www.readbyqxmd.com/read/27775210/g-protein-coupled-receptors-sustained-signaling-via-intracellular-megaplexes-and-pathway-specific-drugs
#1
Andreas Link, Christa E Müller
Together forever? Functional selection was applied to finally achieve separation of the analgesic properties of opiods from serious side effects such as potentially lethal respiratory depression. A Gi-biased μ-opioid-receptor agonist (PZM21) was identified that stabilizes previously unexplored receptor conformations. This compound relieves pain in mice without causing hypoventilation or addiction.
October 24, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27662248/biasing-opioid-receptors-and-cholesterol-as-a-player-in-developmental-biology
#2
Milka Kostic
Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our September 2016 selection includes the discovery of PZM21, a μOR biased agonist with minimal side effects, and the role of cholesterol in Hedgehog signaling pathway.
September 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27533032/structure-based-discovery-of-opioid-analgesics-with-reduced-side-effects
#3
Aashish Manglik, Henry Lin, Dipendra K Aryal, John D McCorvy, Daniela Dengler, Gregory Corder, Anat Levit, Ralf C Kling, Viachaslau Bernat, Harald Hübner, Xi-Ping Huang, Maria F Sassano, Patrick M Giguère, Stefan Löber, Da Duan, Grégory Scherrer, Brian K Kobilka, Peter Gmeiner, Bryan L Roth, Brian K Shoichet
Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids...
August 17, 2016: Nature
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