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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
20 articles
Newest firstMonoacylglycerol lipase (MGL) is an intracellular serine hydrolase that regulates endocannabinoid signaling by hydrolyzing 2‐arachidonoylglycerol (2‐AG), thereby controlling cannabinoid receptor activity and related physiological processes. Targeting MGL through allosteric mechanisms is a promising strategy to modulate 2‐AG levels while avoiding limitations associated with active site–directed inhibitors. In this…
Open article record in new tab ↗Activation of cannabinoid CB1 receptors (CB1R) by agonists induces analgesia but also induces cognitive impairment through the heteromer formed between CB1R and the serotonin 5HT2A receptor (5HT2AR). This side effect poses a serious drawback in the therapeutic use of cannabis for pain alleviation. Peptides designed from the transmembrane helices of CB1R, which are predicted to bind 5HT2AR and alter the stability o…
Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)- and reactive oxygen species (ROS)-targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2'-chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti…
Nowadays, the identification of agonists and antagonists represents a great challenge in computer-aided drug design. In this work, we developed a computational protocol enabling us to design/screen novel chemicals that are likely to serve as selective CB2 agonists. The principle of this protocol is that by calculating the ligand-residue interaction profile (LRIP) of a ligand binding to a specific target, the agoni…
Homeostasis of the host immune system is regulated by white blood cells with a variety of cell surface receptors for cytokines. Chemotactic cytokines (chemokines) activate their receptors to evoke the chemotaxis of immune cells in homeostatic migrations or inflammatory conditions towards inflamed tissue or pathogens. Dysregulation of the immune system leading to disorders such as allergies, autoimmune diseases, or…
Open article record in new tab ↗Nowadays, neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge in different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology and medicine, as all these pathologies remain incurable, with high socioeconomic impacts and high costs for governmenta…
Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The devel…
A series of novel cannabinoid-type derivatives were synthesized by the coupling of (1S,4R)-(+) and (1R,4S)-(-)-fenchones with various resorcinols/phenols. The fenchone-resorcinol derivatives were fluorinated using Selectfluor and demethylated using sodium ethanethiolate in dimethylformamide (DMF). The absolute configurations of four compounds were determined by X-ray single crystal diffraction. The fenchone-resorc…
Although the 3D structures of active and inactive cannabinoid receptors type 2 (CB2) are available, neither the X-ray crystal nor the cryo-EM structure of CB2-orthosteric ligand-modulator has been resolved, prohibiting the drug discovery and development of CB2 allosteric modulators (AMs). In the present work, we mainly focused on investigating the potential allosteric binding site(s) of CB2. We applied different a…
Design and generation of high-quality target- and scaffold-specific small molecules is an important strategy for the discovery of unique and potent bioactive drug molecules. To achieve this goal, authors have developed the deep-learning molecule generation model (DeepMGM) and applied it for the de novo molecular generation of scaffold-focused small-molecule libraries. In this study, a recurrent neural network (RNN…
Open article record in new tab ↗In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer's disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspe…
Open article record in new tab ↗The Sterling Research Group identified pravadoline as an aminoalkylindole (AAI) non-steroidal anti-inflammatory pain reliever. As drug design progressed, the ability of AAI analogs to block prostaglandin synthesis diminished, and antinociceptive activity was found to result from action at the CB1 cannabinoid receptor, a G-protein-coupled receptor (GPCR) abundant in the brain. Several laboratories applied computati…
Open article record in new tab ↗Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthet…
Fatty acid amide hydrolase (FAAH) is a membrane-bound homodimeric enzyme that in vivo controls content and biological activity of N-arachidonoylethanolamine (AEA) and other relevant bioactive lipids termed endocannabinoids. Parallel orientation of FAAH monomers likely allows both subunits to simultaneously recruit and cleave substrates. Here, we show full inhibition of human and rat FAAH by means of enzyme inhibit…
Open article record in new tab ↗[This corrects the article DOI: 10.3389/fphar.2018.01202.].
Open article record in new tab ↗Two 3D quantitative structure⁻activity relationships (3D-QSAR) models for predicting Cannabinoid receptor 1 and 2 (CB₁ and CB₂) ligands have been produced by way of creating a practical tool for the drug-design and optimization of CB₁ and CB₂ ligands. A set of 312 molecules have been used to build the model for the CB₁ receptor, and a set of 187 molecules for the CB₂ receptor. All of the molecules were recovered f…
Cannabinoid receptor 2 (CB2) is predominantly distributed in immune tissues and cells and is a promising therapeutic target for modulating inflammation. In this study we designed and synthesised a series of 2,4,6-trisubstituted 1,3,5-triazines with piperazinylalkyl or 1,2-diethoxyethane (PEG2) chains as CB2 agonists, all of which were predicted to be considerably more polar than typical cannabinoid ligands. In thi…
Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diar…
Open article record in new tab ↗Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-hept…