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Article
Open AccessStructural basis for selectivity and antagonism in extracellular GPCR-nanobodies
G protein-coupled receptors (GPCRs) are pivotal therapeutic targets, but their complex structure poses challenges for effective drug design. Nanobodies, or single-domain antibodies, have emerged as a promising...
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Article
Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala
Psychedelics such as psilocybin show great promise for the treatment of depression and PTSD, but their long duration of action poses practical limitations for patient access. 4-OH-DiPT is a fast-acting and sho...
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Article
Author Correction: PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome
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Article
Open AccessIdentification of 5-HT2A receptor signaling pathways associated with psychedelic potential
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT2A-Gq/11 and β-arrestin2 transdu...
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Article
Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity
There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally1–4. Efforts have focused on readily synthesizable molecules, inevitably leaving...
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Article
(2-Aminopropyl)benzo[β]thiophenes (APBTs) are novel monoamine transporter ligands that lack stimulant effects but display psychedelic-like activity in mice
Derivatives of (2-aminopropyl)indole (API) and (2-aminopropyl)benzofuran (APB) are new psychoactive substances which produce stimulant effects in vivo. (2-Aminopropyl)benzo[β]thiophene (APBT) is a novel sulfur...
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Article
Structure, function and pharmacology of human itch GPCRs
The MRGPRX family of receptors (MRGPRX1–4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological media...
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Article
A non-hallucinogenic psychedelic analogue with therapeutic potential
The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals1. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the p...
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Article
TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome
G-protein-coupled receptors (GPCRs) remain major drug targets, despite our incomplete understanding of how they signal through 16 non-visual G-protein signal transducers (collectively named the transducerome) ...
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Article
Virtual discovery of melatonin receptor ligands to modulate circadian rhythms
The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from th...
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Article
Publisher Correction: Structural basis of ligand recognition at the human MT1 melatonin receptor
Change history: In this Letter, the rotation signs around 90°, 135° and 15° were missing and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online.
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Article
Structural basis of ligand recognition at the human MT1 melatonin receptor
Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms1 by synchronization to environmental cues and is involved in diverse physiological processes2 such as the regulation of ...
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Article
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
The human MT1 and MT2 melatonin receptors1,2 are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns3. Drug development efforts have targeted both receptors for the treat...
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Article
Structural determinants of 5-HT2B receptor activation and biased agonism
Serotonin (5-hydroxytryptamine; 5-HT) receptors modulate a variety of physiological processes ranging from perception, cognition and emotion to vascular and smooth muscle contraction, platelet aggregation, gas...
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Article
Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs
D2 dopamine receptor ligands biased for b-arrestin recruitment were developed based on a receptor homology model that identified conserved ligand contacts within the TM5 and EL2 regions as important for biased...
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Article
Open AccessThe anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand
Schistosomiasis is a debilitating tropical disease caused by infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact o...
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Article
In silico design of novel probes for the atypical opioid receptor MRGPRX2
High-throughput screening identifies opioid compounds and prodynorphin-derived peptide agonists of the G-protein-coupled receptor MRGPRX2 and informs a homology model that is used for in silico screening to find ...
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Article
Structure-based discovery of opioid analgesics with reduced side effects
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-o...
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Article
PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome
Roth and colleagues have developed PRESTO-Tango, a new open-source platform for high-throughput screening of the entire human nonolfactory GPCRome, and they show how it can be used to identify new ligands for ...
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Article
Comparison of the D1 dopamine full agonists, dihydrexidine and doxanthrine, in the 6-OHDA rat model of Parkinson's disease
Preclinical evidence indicates that D1 dopamine receptor full agonists have potential as therapeutic agents for a variety of neurological conditions. Dihydrexidine (DHX) was the first high potency selective D1 do...
