All Outputs (59)

Enantioselective de novo synthesis of 14-hydroxy-6-oxomorphinans (2024)
Journal Article

The enantioselective de novo synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors wer... Read More about Enantioselective de novo synthesis of 14-hydroxy-6-oxomorphinans.

Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3) (2023)
Journal Article

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluoresc... Read More about Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3).

Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity (2023)
Journal Article

The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties of receptor activatio... Read More about Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity.

Assessment of the potential of novel and classical opioids to induce respiratory depression in mice (2023)
Journal Article

Background and Purpose Opioid-induced respiratory depression limits the use of μ-opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respira... Read More about Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics (2023)
Journal Article

A new generation of dual-target μ opioid receptor (MOR) agonist/dopamine D3 receptor (D3R) antagonist/partial agonists with optimized physicochemical properties was designed and synthesized. Combining in vitro cell-based on-target/off-target affinity... Read More about Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.

OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz (2022)
Journal Article

Heterotrimeric G proteins are the main signalling effectors for G protein-coupled receptors. Understanding the distinct functions of different G proteins is key to understanding how their signalling modulates physiological responses. Pertussis toxin,... Read More about OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz.

The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine (2022)
Journal Article

Background and Purpose: Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), is a partial agonist at the μ opioid receptor. CYP3A-dependent oxidation of mitragynine yields the metabolite 7-OH mitragynine, a more efficacious μ receptor agon... Read More about The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine.

Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders (2021)
Journal Article

Allosteric modulators (AMs) are molecules that can fine-tune signaling by G protein-coupled receptors (GPCRs). Although they are a promising therapeutic approach for treating a range of disorders, allosteric modulation of GPCRs in the context of the... Read More about Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders.

Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia (2021)
Journal Article

Introduction: Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises.... Read More about Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia.

Atypical opioid receptors: unconventional biology and therapeutic opportunities (2021)
Journal Article

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating four opioid receptors, namely μ (mu, MOP), δ (delta, DOP), κ (kappa, KOP) and the nociceptin/orphanin FQ receptor (NOP). Interestingly, several o... Read More about Atypical opioid receptors: unconventional biology and therapeutic opportunities.

Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology (2021)
Journal Article

Morphine and other mu-opioid receptor (MOR) agonists remain the mainstay treatment of acute and prolonged pain states worldwide. The major limiting factor for continued use of these current opioids is the high incidence of side effects that result in... Read More about Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology.

Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management (2021)
Journal Article

The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopami... Read More about Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14 (2021)
Journal Article

Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1–74), is a weak agonist for the chemokine receptor CCR1, but its act... Read More about Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14.

Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10 (2021)
Journal Article

Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the... Read More about Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10.

New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling (2021)
Journal Article

The dopamine D2 receptor (D2R) is the target of drugs used to treat the symptoms of Parkinson’s disease and schizophrenia. The D2R is regulated through its interaction with and phosphorylation by G protein receptor kinases (GRKs) and interaction with... Read More about New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling.

A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes (2021)
Journal Article

G-protein-coupled receptors (GPCRs) are traditionally known for signaling at the plasma membrane, but they can also signal from endosomes after internalization to control important pathophysiological processes. In spinal neurons, sustained endosomal... Read More about A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes.

GRKs as Key Modulators of Opioid Receptor Function (2020)
Journal Article

Understanding the link between agonist-induced phosphorylation of the mu-opioid receptor (MOR) and the associated physiological effects is critical for the development of novel analgesic drugs and is particularly important for understanding the mecha... Read More about GRKs as Key Modulators of Opioid Receptor Function.

The life cycle of the Mu-Opioid Receptor (2020)
Journal Article

Opioid receptors are undisputed targets for the treatment of pain. Unfortunately, targeting these receptors therapeutically poses significant challenges including addiction, dependence, tolerance and the appearance of side-effects such as respiratory... Read More about The life cycle of the Mu-Opioid Receptor.

Critical assessment of G protein-biased agonism at the µ opioid receptor (2020)
Journal Article

G protein-biased agonists of the µ-opioid receptor have been proposed to be an improved class of opioid analgesics. Recent studies have been unable to reproduce the original experiments in the β-arrestin2 knockout mouse that led to this proposal, and... Read More about Critical assessment of G protein-biased agonism at the µ opioid receptor.

Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain (2020)
Journal Article