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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.
58 articles
Newest firstSynthetic cannabinoids (SC) target the human cannabinoid receptor 1 (hCB1) and are extensively metabolized, but the metabolite activity on the hCB1 receptor after a SC intake is largely unknown. In this study we compared the in vitro hCB1 receptor activity of 26 metabolites of the synthetic cannabinoid receptor agonists (SCRA) JWH-018, AM-2201, THJ-018 and THJ-2201 as a model system for SC metabolite activity to e…
Open article record in new tab ↗The development of peripherally selective cannabinoid-1 receptor (CB1R) antagonists offers a promising strategy for obesity treatment. Here, we evaluated the efficacy of novel tricyclic CB1R antagonists, focusing on BNS808. Our findings demonstrate that BNS808 exhibits robust CB1R antagonism with notable CB2R selectivity, minimal brain penetration, and potent in vitro and in vivo efficacy. The compound's high plas…
Open article record in new tab ↗CB1 agonist compounds may be potential drug candidates for the treatment of gliomas, as they have been shown to inhibit tumor cell proliferation, induce apoptosis, and reduce angiogenesis in various preclinical models. Their ability to modulate the endocannabinoid system suggests a promising therapeutic approach for targeting glioma growth and progression. Herein, we report the design, synthesis, biological studie…
The rapid structural evolution and extensive metabolism of synthetic cannabinoid receptor agonists (SCRAs) following consumption makes their detection in biological samples challenging, especially in urine. In vitro metabolite identification studies are an essential tool for identifying analytical targets to confirm SCRA consumption in clinical and forensic toxicology casework. Systematic studies on structurally r…
Aberrant wound healing in the retina can manifest as proliferative vitreoretinopathy (PVR), which involves the myofibroblast transdifferentiation of retinal pigment epithelial (RPE) cells. In this study, experiments were conducted to examine the structure-activity relationships of endocannabinoid-like compounds, N-acyl dopamines, on the myofibroblast transdifferentiation of RPE cells. The collagen matrix contracti…
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…
The cannabinoid receptor type 2 (CB2R) is overexpressed under pathological conditions. Positron emission tomography is a noninvasive imaging technique for diagnosing disease states, but requires radiotracers with high affinity and selectivity towards CB2R. Currently, there is no suitable candidate routinely used in the clinics. The naphthyridinone scaffold, a promising core structure, has been modified in the past…
Open article record in new tab ↗Cannabidiol (CBD), a non-psychoactive cannabinoid, has attracted significant research interest due to its antioxidant, anti-inflammatory, and neuroprotective properties. As a versatile scaffold in drug discovery, CBD has been widely explored for developing novel therapeutics. In this study, we synthesized and evaluated the anti-tyrosinase activity of CBD-based thiosemicarbazones. Structure-activity relationship (S…
Open article record in new tab ↗Structure-activity relationship studies were performed on a library of synthesized compounds based on previously identified tau ligands. The top 13 new compounds had Ki values in the range of 5-14 nM in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One of the more promising new compounds ([3H]75) bound with high affinity in AD, PSP, a…
Synthetic cannabinoids (SCs), a class of widely abused new psychoactive substances, are characterized by their structural diversity and rapid evolution. Structure-affinity relationships are crucial for predicting pharmacological effects and potential toxicity. Traditional methods for affinity testing are often complex and less applicable to newly modified compounds. In contrast, Surface Plasmon Resonance (SPR) is…
Synthetic cannabinoid receptor agonists (SCRAs) are a group of new psychoactive substances (NPS) that bind to and activate the cannabinoid 1 and 2 (CB1 and CB2) receptors. Following the introduction of SCRA analog controls in China in July 2021, new SCRAs with a bromine at the 5 position on the indazole core emerged on the recreational drug market. In this study, the in vitro CB1 receptor activity of 19 different…
Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported LEI-515, an aryl sulfoxide, as a peripherally restricted, covalent rev…
The structure-tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/differe…
The cannabinoid receptor type 1 (CB1R) is pivotal within the endocannabinoid system regulating various signaling cascades with effects in appetite regulation, pain perception, memory formation, and thermoregulation. Still, understanding of CB1R's cellular signaling, distribution, and expression dynamics is very fragmentary. Real-time visualization of CB1R is crucial for addressing these questions. Selective drug-l…
Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is of particular interest, given the cornucopia of natural and synthetic cannabinoids being explored as therapeutics. We show for the first time that engineering the N-terminus of CB1R allows for efficient signal transduction in yeast, and that e…
The type-1 cannabinoid receptor (CB1R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB1R ligands. In this study, CB1R ligands were classified into six structural families, and the corresponding SAR was deter…
Open article record in new tab ↗The development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation under various pathological conditions. Herein, we report on the synthesis of a series of CB2R affine fluorinated indole-2-carboxamide ligands. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (Ki = 2.1 nM) and selectivity over CB1R (fa…
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…
Selective modulation of peripheral cannabinoid receptors (CBRs) has potential therapeutic applications in medical conditions, including obesity, diabetes, liver diseases, GI disorders and pain. While there have been considerable efforts to produce selective antagonists or full agonists of CBRs, there has been limited reports on the development of partial agonists. Partial agonists targeting peripheral CBRs may hav…
Open article record in new tab ↗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…