Article
Biology
Brandon Wey-Hung Liauw, Arash Foroutan, Michael R. Schamber, Weifeng Lu, Hamid Samareh Afsari, Reza Vafabakhsh
Summary: This article investigates the activation process of GPCRs and the mechanism of action of allosteric modulators. The researchers developed FRET sensors to quantify receptor modulation at the structural level in mGluR2. They found that the effect of allosteric modulators on the receptor is complex and depends on the orthosteric ligand. These findings provide possible strategies for the design of future modulators.
Review
Clinical Neurology
Catharine A. Mielnik, Vincent M. Lam, Ruth A. Ross
Summary: CB1 is the most abundant GPCR in the mammalian brain and has garnered attention as a potential therapeutic drug target, although no novel synthetic cannabinoids are currently in clinical use for psychiatric illnesses. Research is ongoing to develop new strategies to target CB1 while minimizing potential psychiatric adverse effects, with a focus on allosteric modulation as one promising approach.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Silvia Pasquini, Chiara Contri, Martina Cappello, Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi
Summary: Adenosine receptors (ARs) have great therapeutic potential for a wide range of pathological conditions. Targeting allosteric sites with allosteric modulators can overcome the limitations of orthosteric ligands. Promising results have been achieved with various allosteric modulators, but more research is needed for certain AR subtypes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tianling Hou, Yuemin Bian, Terence McGuire, Xiang-Qun Xie
Summary: This study focused on multi-class classification of GPCR allosteric modulators, training six machine learning models with different feature combinations. The research found that these models can accurately distinguish different GPCR classes and modulators, showing great potential for research and application.
Article
Biochemistry & Molecular Biology
Jakub Jakowiecki, Renata Abel, Urszula Orzel, Pawel Pasznik, Robert Preissner, Slawomir Filipek
Summary: The N-terminal domain of the CB1 cannabinoid receptor is crucial for the allosteric binding of cannabidiol (CBD) and plays a key role in the stable binding of CBD in the allosteric site. The presence of the complete N-terminal domain is also essential for the allosteric-orthosteric coupling mechanism of CBD in modulating the CB1R.
Article
Biochemistry & Molecular Biology
James P. Farmer, Shailesh N. Mistry, Charles A. Laughton, Nicholas D. Holliday
Summary: This study developed fluorescent-labeled peptides as novel binding and activation biosensors for the GPCR-IAM site, allowing the assessment of the affinity of unlabeled ligands for the receptor and providing a new method for screening IAMs. Moreover, this method can be used to investigate the efficacy of orthosteric agonists and the dynamics of receptor activation.
Article
Biochemistry & Molecular Biology
Thuy Nguyen, Thomas F. Gamage, Ann M. Decker, David B. Finlay, Tiffany L. Langston, Daniel Barrus, Michelle Glass, Danni L. Harris, Yanan Zhang
Summary: The research found that two CB1 negative allosteric modulators have similar structural and activity relationships, and designed a new scaffold that retains key binding features in molecular docking studies. The new hybrids showed comparable potencies to existing negative allosteric modulators in experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jennifer M. Clark, Fernando Salgado-Polo, Simon J. F. Macdonald, Tim N. Barrett, Anastassis Perrakis, Craig Jamieson
Summary: The study designed and synthesized a series of novel steroid-derived analogues targeting the bimetallic catalytic site as ATX inhibitors. These inhibitors modulated LPA-mediated signaling and cell chemotaxis, demonstrating significant pathway-relevant biological effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Nutrition & Dietetics
Edmund Przegalinski, Kacper Witek, Karolina Wydra, Jolanta H. Kotlinska, Malgorzata Filip
Summary: Obesity is a significant health and economic issue, and the serotonin system, specifically the 5-HT2C receptors, plays a crucial role in regulating body weight. This review focuses on the use of 5-HT2C receptor agonists as antiobesity medications, such as fenfluramines, sibutramine, and lorcaserin, and discusses the potential of 5-HT2C receptor positive allosteric modulators as safer alternatives. More research is needed to determine the efficacy of these drugs in obesity prevention and treatment.
Article
Chemistry, Medicinal
Lucas B. Fallot, R. Rama Suresh, Courtney L. Fisher, Veronica Salmaso, Robert D. O'Connor, Noy Kaufman, Zhan-Guo Gao, John A. Auchampach, Kenneth A. Jacobson
Summary: In this study, we synthesized new analogues to distinguish between 2-cyclopropyl antagonists and derivatives with large alkyl/cycloalkyl/bicycloalkyl groups as positive allosteric modulators (PAMs) for A3 adenosine receptor (A3AR). We predicted the binding of PAMs at a hydrophobic site on the A3AR cytosolic interface. Some derivatives, such as 2-cyclohept-4-enyl-N-3,4-dichlorophenyl and 2-heptan-4-yl-N-4-iodophenyl, showed good oral bioavailability in rats and significantly enhanced the binding effect of Cl-IB-MECA stimulation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yonglei Du, Feng Gao, Hongwei Sun, Chenglin Wu, Guoqi Zhu, Manzhou Zhu
Summary: mGlu5 is a potential drug target for the treatment of depression, but no small molecule mGlu5 NAM has reached the market yet. This study reports the structural optimization and structure-activity relationship studies of a series of novel mGlu5 NAMs. Among them, compound 10b is a high-affinity mGluR5 antagonist and has shown anti-depressant effects in a depression model. Preliminary toxicology evaluations indicate that compound 10b has good safety profile in vivo. Therefore, compound 10b represents a promising lead compound for the treatment of depressive disorder.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Computer Science, Interdisciplinary Applications
Lifang Yang, Jinsen Guo, Yong-Wu Zhou, Bin Cao
Summary: This study examines the pricing and selling format selection problem for e-platforms in two competing online-to-offline supply chains, finding that spillover effect plays a key role in format selection and results in lower prices. Lower commission rates make agency selling arrangement unfavorable, while higher rates tie format selection closely to spillover effects.
COMPUTERS & INDUSTRIAL ENGINEERING
(2021)
Article
Chemistry, Medicinal
Thuy Nguyen, Thomas F. Gamage, David B. Finlay, Ann M. Decker, Tiffany L. Langston, Daniel Barrus, Michelle Glass, Jun-Xu Li, Terry P. Kenakin, Yanan Zhang
Summary: This study demonstrated that CB1 receptor negative allosteric modulators attenuated cocaine-seeking behaviors in rats. By introducing substituents with different properties to the phenethyl group, the potency of CB1 NAMs was evaluated. The 3-chloro analogue showed promising results in selectively attenuating cocaine-seeking behavior without affecting locomotion.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sofia Papadogkonaki, Dimitris Spyridakos, Emmanouela Lapokonstantaki, Nikos Chaniotakis, Alexandros Makriyannis, Michael Malamas, Kyriaki Thermos
Summary: The endocannabinoid 2-arachidonoylglycerol (2-AG) affects neurons and microglia by activating CB1/CB2 cannabinoid receptors (Rs), showing neuroprotective and anti-inflammatory effects. The study found that the effects of 2-AG on CB1R expression/downregulation and neuroprotection differ depending on the mode of administration. However, all treatments attenuated microglial activation via CB2R activation, supporting the anti-inflammatory role of 2-AG in the retina.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agricultural Economics & Policy
Ying Song, Wenyu Wu, Dario Miocevic
Summary: This study demonstrates the importance of aligning a farmer's choice between endogenous and exogenous e-commerce platforms with external and internal resources, as well as with their performance goals. Farmers relying on exogenous platforms should seek support from agricultural cooperatives for market expansion, while farmers aiming for a price premium should focus on developing their own e-commerce platforms and emphasizing quality labels.
BRITISH FOOD JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Maria Maisto, Vincenzo Piccolo, Ettore Novellino, Elisabetta Schiano, Fortuna Iannuzzo, Roberto Ciampaglia, Vincenzo Summa, Gian Carlo Tenore
Summary: The study optimized the extraction process of Ursolic acid (UA) from Annurca apple (AA) using sunflower oil as a solvent, and identified twenty-three phenolic and terpenoid molecules in the extract. The optimized extract, named Optimized Annurca Apple Oleolyte (OAAO), showed significant antioxidant activity and could be considered a safe and functional ingredient for cosmetic formulations.
Article
Biochemistry & Molecular Biology
Karishma Kundu, Roberta Teta, Germana Esposito, Mariano Stornaiuolo, Valeria Costantino
Summary: This study proposes a four-step experimental pipeline for the rapid and inexpensive identification and optimization of growth parameters influencing siderophore production in Anabaena flos aquae. The pipeline is multidisciplinary, sustainable, and applicable to any cyanobacteria or microorganism.
Article
Biochemistry & Molecular Biology
Giuseppina Chianese, Annalisa Lopatriello, Carmina Sirignano, Alessandro Andreani, Andrea Gambini, Eric De Combarieu, Mariano Stornaiuolo, Orazio Taglialatela-Scafati
Summary: Two unprecedented cyclopamine analogues, 18-hydroxycyclopamine and 24R-hydroxycyclopamine, with modifications on rings D-F, were isolated from the mother liquors obtained from crystallization of cyclopamine extracted from corn lily. The stereostructures of these new natural compounds were determined through detailed MS and 1D/2D NMR investigation. Their inhibition of the hedgehog pathway was evaluated using the dual-luciferase bioassay, providing new insights into the structure-activity relationships for this class of compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Maria Maisto, Fortuna Iannuzzo, Ettore Novellino, Elisabetta Schiano, Vincenzo Piccolo, Gian Carlo Tenore
Summary: Urinary tract infections (UTIs) are a common bacterial infection, especially in women. The main etiological agents are E. coli, Pseudomonas aeruginosa, and Proteus mirabilis. Due to the increase in antimicrobial resistance, there is a need for natural alternatives for UTI treatment. This review summarizes the potential therapeutic effects of natural polyphenol-based nutraceuticals and foods through in vitro and in vivo studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Serena Sagliocchi, Melania Murolo, Annunziata Gaetana Cicatiello, Caterina Miro, Annarita Nappi, Emery Di Cicco, Sepehr Torabinejad, Evelina La Civita, Veronica Romano, Daniela Terracciano, Mariano Stornaiuolo, Monica Dentice
Summary: The iodothyronine deiodinases are a group of enzymes that regulate thyroid hormone metabolism and affect various physiological processes. Deregulation of these enzymes is associated with several human pathologies. This study identifies Cefuroxime as a novel inhibitor of D2 activity, potentially offering a new treatment option for hyperthyroid pathologies.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Food Science & Technology
Francesco Errichiello, Maria 'Amato, Angelita Gambuti, Luigi Moio, Arianna Pastore, Hekmat AL-Hmadi, Mariano Stornaiuolo, Elena Serino, Orazio Taglialatela-Scafati, Martino Forino
Summary: Grape pomace, a component of winery waste, contains various healthy compounds with bioactivities. In addition to polyphenols, an in-depth chemical analysis of Aglianico grape pomace revealed a remarkable concentration of oleanolic acid, a natural triterpenoid with multiple bioactivities. The study also assessed the influence of oleanolic acid on mitochondrial and glucose uptake activities, supporting its potential as an antidiabetic metabolite.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Multidisciplinary Sciences
Annarita Nappi, Caterina Miro, Antonio Pezone, Alfonso Tramontano, Emery Di Cicco, Serena Sagliocchi, Annunziata Gaetana Cicatiello, Melania Murolo, Sepehr Torabinejad, Elena Abbotto, Giuseppina Caiazzo, Maddalena Raia, Mariano Stornaiuolo, Dario Antonini, Gabriella Fabbrocini, Domenico Salvatore, Vittorio Enrico Avvedimento, Monica Dentice
Summary: In this study, the authors investigate the role of thyroid hormones in tumor progression and identify the thyroid hormone activating enzyme D2 as a p53 target gene. They find that p53, as a cell stress sensor and tumor suppressor, suppresses D2 expression, leading to decreased availability of intracellular thyroid hormones. Conversely, loss of p53 enhances D2/TH signaling, promoting the fitness of tumor cells through modulation of genes involved in DNA damage and repair and redox signaling. In vivo deletion of D2 significantly reduces cancer progression, suggesting that targeting thyroid hormones could be a general approach to reduce invasiveness in p53-mutated neoplasms.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Giovanni Smaldone, Elisabetta Rosa, Enrico Gallo, Carlo Diaferia, Giancarlo Morelli, Mariano Stornaiuolo, Antonella Accardo
Summary: Hydrogel nanoparticles, also called nanogels, can be used as supramolecular vehicles for delivering biologically relevant molecules. Understanding the intracellular mechanism of nanogel uptake by cancer cells can contribute to their potential diagnostic and clinical applications.
Article
Biochemistry & Molecular Biology
Elisabetta Schiano, Enrico Cappello, Domenico Cecere, Francesco Pompeo, Ettore Novellino, Mariano Stornaiuolo, Marcello Izzo
Summary: Under pathological conditions, the level of Non-Transferrin Bound Iron (NTBI) in the blood increases, leading to oxidative stress and damage to organs and tissues. This study focuses on measuring and analyzing the NTBI pool in the serum of peripheral arterial disease (PAD) patients. The researchers found that NTBI in PAD patients is predominantly bound to the serum protein Albumin, and developed a simple immunoisolation procedure to quantify NTBI-Albumin complexes for clinical screening purposes.
Article
Microbiology
Carla Zannella, Annalisa Chianese, Giuseppe Annunziata, Annalisa Ambrosino, Anna De Filippis, Gian Carlo Tenore, Ettore Novellino, Mariano Stornaiuolo, Massimiliano Galdiero
Summary: Herpes simplex virus (HSV) is a common virus that causes oral or genital ulcers and can lead to severe complications. Current anti-HSV drugs have limitations, so there is a need for new antiviral compounds. This study tested a polyphenol-based nutraceutical formulation called Taurisolo(R), which showed potential in inhibiting the early stages of HSV-1 and HSV-2 infection. These findings suggest that Taurisolo(R) could be used as a topical treatment for preventing and healing herpes lesions.
Article
Food Science & Technology
Giorgia Musto, Elisabetta Schiano, Fortuna Iannuzzo, Gian Carlo Tenore, Ettore Novellino, Mariano Stornaiuolo
Summary: Agri-food by-products contribute to pollution when disposed incorrectly, but can be recycled as alternative raw material for bioactive compound extraction. Safety assessment is crucial due to chemical complexity. In this study, two nutraceutical products obtained from food waste were evaluated for mutagenicity using the Ames and micronucleus test. Results show that the products are genotoxically safe up to specific doses, complying with safety regulations.
Article
Food Science & Technology
Elisabetta Schiano, Ilaria Neri, Maria Maisto, Ettore Novellino, Fortuna Iannuzzo, Vincenzo Piccolo, Vincenzo Summa, Lucia Grumetto, Gian Carlo Tenore
Summary: This study developed and validated a method for measuring abscisic acid (ABA) in biological samples using liquid-liquid extraction and liquid mass spectrometry. The researchers found that ABA plays a role in regulating glucose homeostasis in humans, as evidenced by its increase after consuming a standardized test meal. This finding is important for the treatment and monitoring of individuals with dysglycemia.
Article
Biochemistry & Molecular Biology
Aurore Fraix, Cristina Parisi, Giuseppe Longobardi, Claudia Conte, Arianna Pastore, Mariano Stornaiuolo, Adriana C. E. Graziano, Marta E. E. Alberto, Antonio Frances-Monerris, Fabiana Quaglia, Salvatore Sortino
Summary: Activation of nitric oxide (NO) release in the red-light range using a green-light excitation method has been demonstrated. This method allows for precise control of NO release without the need for chemical modification or sophisticated irradiation sources. The effectiveness of this strategy has been confirmed in a biological environment, making it a potential candidate for nanotherapeutics.
Article
Chemistry, Medicinal
Elisabetta Barresi, Caterina Baldanzi, Marta Roncetti, Michele Roggia, Emma Baglini, Irene Lepori, Marianna Vitiello, Silvia Salerno, Lorena Tedeschi, Federico Da Settimo, Sandro Cosconati, Laura Poliseno, Sabrina Taliani
Summary: BRAF is a frequently mutated protein kinase gene, and BRAFV600E mutation can be found in various types of cancer. Researchers synthesized a fluorescent probe that specifically binds to BRAFV600E and demonstrated its promising spectroscopic properties. The probe is able to penetrate inside the cells, inhibit MEK phosphorylation and cell growth, with comparable potency to the native inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Caterina Miro, Annarita Nappi, Serena Sagliocchi, Emery Di Cicco, Melania Murolo, Sepehr Torabinejad, Lucia Acampora, Arianna Pastore, Paolo Luciano, Evelina La Civita, Daniela Terracciano, Mariano Stornaiuolo, Monica Dentice, Annunziata Gaetana Cicatiello
Summary: Thyroid hormones play a role in regulating muscle formation and energy utilization by modulating carbohydrates, lipids, and proteins. They can change the lipid composition and fatty acid ratio in skeletal muscle, with increased proportion of unsaturated fatty acids improving insulin sensitivity and endurance exercise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
