A5011170921- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Synthetic Organic Chemistry Methods
- Herbal Medicine Research Studies
- Cancer Treatment and Pharmacology
- Neurotransmitter Receptor Influence on Behavior
- Toxin Mechanisms and Immunotoxins
- Pharmacological Receptor Mechanisms and Effects
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- GABA and Rice Research
- X-ray Diffraction in Crystallography
- Traditional and Medicinal Uses of Annonaceae
- Crystallization and Solubility Studies
- Forensic Toxicology and Drug Analysis
- Microtubule and mitosis dynamics
- Bioactive Compounds and Antitumor Agents
- Psychedelics and Drug Studies
- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Trypanosoma species research and implications
- Amino Acid Enzymes and Metabolism
- Microbial Natural Products and Biosynthesis
- Phytochemistry and Biological Activities
- Tryptophan and brain disorders
University of Bern
2016-2025
ETH Zurich
2002-2013
University of Cagliari
2006-2013
Universidade de Santiago de Compostela
2012
École Polytechnique Fédérale de Lausanne
2002-2011
University of Turin
2011
Pierre Fabre (France)
2010
Novartis Institutes for BioMedical Research
2008
Max Planck Institute for Biophysical Chemistry
2008
Inte:Ligand (Austria)
2008
The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) CB(2) receptors. Although CB(1) is responsible psychomodulatory effects, activation of a potential therapeutic strategy treatment inflammation, pain, atherosclerosis, osteoporosis. Here, we report that widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to (K(i) = 155 +/- 4 nM) it functional...
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links open access knowledgebase source and their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes over 500 pages, material presented substantially reduced compared...
Abstract The cannabinoid CB 2 receptor (CB R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed widely used to R, their selectivity, molecular mode action pharmacokinetic properties poorly characterized. Here we report the most extensive characterization pharmacology R ligands date. In collaborative effort between multiple academic industry laboratories, identify marked differences in...
The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations many spices and food plants. A number studies have shown that CB₂ critically involved modulation inflammatory neuropathic pain responses. In this study, we investigated analgesic effects BCP animal models pain. We demonstrate orally administered reduced (late phase) responses...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and about 6000 interactions with 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes almost 500 pages,...
Alkylamides (alkamides) from Echinacea modulate tumor necrosis factor α mRNA expression in human monocytes/macrophages via the cannabinoid type 2 (CB2) receptor (Gertsch, J., Schoop, R., Kuenzle, U., and Suter, A. (2004) FEBS Lett. 577, 563–569). Here we show that alkylamides dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (A1) dodeca-2E,4E-dienoic (A2) bind to CB2 more strongly than endogenous cannabinoids. The Ki values of A1 A2 (CB2 ∼60 nm;CB1 >1500 nm) were determined by displacement...
Echinacea plant preparations are widely used in the prevention and treatment of common cold. However, so far no molecular mechanism action has been proposed. We analyzed standardized tincture Echinaforce found that it induced de novo synthesis tumor necrosis factor alpha (TNF-alpha) mRNA primary human monocytes/macrophages, but not TNF-alpha protein. Moreover, LPS-stimulated protein was potently inhibited early phase prolonged late phase. A study main constituents extract showed alkylamides...
Mild control: Selective cyclization of aminocyclopropanes at either the N1 or C3 position an indole ring was achieved by tuning reaction conditions (see scheme). This strategy applied to formal synthesis aspidospermidine and total goniomitine, which demonstrated significant cytotoxicity against several tumor cell lines (IC50=150–400 nM). Cbz=benzyloxycarbonyl, Ts=4-toluenesulfonyl. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents...
GABA A receptors are the major ionotropic inhibitory neurotransmitter receptors. The endocannabinoid system is a lipid signaling network that modulates different brain functions. Here we show direct molecular interaction between two systems. 2-arachidonoyl glycerol (2-AG) potentiates at low concentrations of GABA. Two residues receptor located in transmembrane segment M4 β 2 confer 2-AG binding. acts superadditive fashion with neurosteroid 3α, 21-dihydroxy-5α-pregnan-20-one (THDOC) and...
The α-hemoglobin-derived dodecapeptide RVD-hemopressin (RVDPVNFKLLSH) has been proposed to be an endogenous agonist for the cannabinoid receptor type 1 (CB1). To study this peptide, we have raised mAbs against its C-terminal part. Using immunoaffinity mass spectrometry approach, a whole family of N-terminally extended peptides in addition RVD-Hpα were identified rodent brain extracts and human mouse plasma. We designated these Pepcan-12 Pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH), referring peptide...
GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also certain cannabinoids. In this study, we investigated the pharmacology of various cannabinoids, including analogues CB1 receptor antagonist Rimonabant®, CB2 agonists, and Cannabis sativa constituents. To test ERK1/2 phosphorylation, a primary downstream signaling pathway that conveys LPI-induced activation GPR55, high throughput system, was established using AlphaScreen® SureFire® assay. Here, show antagonists can act both as...
Despite extensive research on the trafficking of anandamide (AEA) across cell membranes, little is known about membrane transport other endocannabinoids, such as 2-arachidonoylglycerol (2-AG). Previous studies have provided data both in favor and against a carrier-mediated using different methodological approaches. Because AEA 2-AG undergo rapid almost complete intracellular hydrolysis, we employed combination radioligand assays absolute quantification cellular extracellular endocannabinoid...
Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities cognitive deficits commonly observed psychiatric disorders. Here, we report identification a subset cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal prefrontal cortex (PFC), allowing optimal DA-mediated maturation excitatory circuits. Such control DA...
Significance Suitable chemical tools have been instrumental in the discovery and characterization of endocannabinoid system. However, lack potent selective inhibitors for transport has prevented molecular this process. Current uptake are poorly bioavailable to central nervous system (CNS) weakly because they also inhibit fatty acid amide hydrolase (FAAH), major anandamide-degrading enzyme. Few studies addressed inhibition 2-arachidonoyl glycerol (2-AG), which is endocannabinoid. Here, we...
The L-type amino acid transporter 1 (LAT1/SLC7A5) transports essential acids across the plasma membrane. While LAT1 is overexpressed in a variety of human neoplasms, its expression and role thyroid cancer currently unknown. Anaplastic carcinoma (ATC) highly aggressive malignancy for which no effective therapy exists. purpose this study was to explore whether inhibition ATC would affect tumor growth both vitro vivo. pharmacologically blocked by JPH203 papillary (PTC) cell lines. effects on...
Abstract LAT1 (SLC7A5) is one of the representative light chain proteins heteromeric amino acid transporters, forming a heterodimer with its heavy partner 4F2hc (SLC3A2). overexpressed in many types tumors and mediates transfer drugs hormones across blood-brain barrier. Thus, considered as drug target for cancer treatment may be exploited delivery into brain. Here, we synthesized three potent inhibitors human LAT1, which inhibit transport leucine IC 50 values between 100 250 nM, solved...