Article
Multidisciplinary Sciences
J. D. Gross, D. W. Kim, Y. Zhou, D. Jansen, L. M. Slosky, N. B. Clark, C. R. Ray, X. Hu, N. Southall, A. Wang, X. Xu, E. Barnaeva, W. C. Wetsel, M. Ferrer, J. J. Marugan, M. G. Caron, L. S. Barak, K. Toth
Summary: This study discovered a novel GHSR(1a) agonist called N8279, which exhibits strong selectivity for G protein signaling, providing potential for treating disorders of disrupted dopamine homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Clinical Neurology
Jose Fidel Baizabal-Carvallo, John C. Morgan
Summary: Tremor is a common movement disorder with numerous causes, including drug-induced tremors. Discontinuation of the offending drug usually resolves drug-induced tremors, but persistent tremors may occur in some cases.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jingyi Zhao, Vincent DiGiacomo, Mariola Ferreras-Gutierrez, Shiva Dastjerdi, Alain Ibanez de Opakua, Jong-Chan Park, Alex Luebbers, Qingyan Chen, Aaron Beeler, Francisco J. Blanco, Mikel Garcia-Marcos
Summary: IGGi-11 selectively inhibits noncanonical activation of heterotrimeric G-protein signaling, blocking tumor cell signaling and inhibiting metastatic cancer cell invasion without interfering with canonical GPCR signaling mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Qi Liang, Xue Zhao, Xiaoying Fu, Jing Wang, Qian Li, Xinfeng Zhao
Summary: The study utilized receptor-affinity chromatography and high-throughput sequencing techniques for rapid screening and identification of specific ligands, finding that the kinetic and thermodynamic parameters of these ligands are similar to positive drugs, making them promising drug candidates.
BIOORGANIC CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Attila Egyed, Dora Judit Kiss, Gyorgy M. Keseru
Summary: G-protein coupled receptors (GPCRs) are important therapeutic targets, with class A receptors representing the largest group and having the highest number of validated drug targets. In addition to the orthosteric binding pocket, secondary binding pocket (SBP) located in the extracellular vestibule also plays a role in modulating the pharmacology of the receptors. SBP binders significantly contribute to the pharmacological profile of bitopic ligands.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Maria Buur Nordskov Gabe, Laerke Smidt Gasbjerg, Sarina Gadgaard, Peter Lindquist, Jens Juul Holst, Mette Marie Rosenkilde
Summary: This study investigates the regulatory role of the GLP-2 system in the gut and bones by studying the effects of N-terminal truncations of human GLP-2 peptides on GLP-2 receptor activity and selectivity. The results show that the N-terminus of GLP-2 is crucial for GLP-2 receptor activity and selectivity. These findings provide a foundation for the development of tool compounds for further characterization of the GLP-2 system.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lukas Zell, Alina Bretl, Veronika Temml, Daniela Schuster
Summary: Different dopamine receptor subtypes are involved in various conditions, and this study identified novel ligands with high affinity and selectivity for D2R/D3R. In vitro experiments and in silico analysis were used to rationalize the ligands' selectivity and interaction with secondary binding pockets. This research contributes to the understanding of structural motifs responsible for DR subtype selectivity and can aid drug development in D2R/D3R-associated pathologies.
Review
Biochemistry & Molecular Biology
Abhilash Rana, Seema Bhatnagar
Summary: This review discusses the importance of targeted delivery and controlled release of drugs in personalized medicine, particularly in the context of cancer treatment. It outlines the principles, advantages, drawbacks, and criteria for designing small molecule-drug conjugates (SMDCs) to achieve therapeutic potency with minimal toxicity. Additionally, it covers the selection of tumor specific receptors, optimal elements in design, therapeutic drug payload, spacer, linker chemistries, and cleavage strategies for SMDCs. The review also touches upon folate receptor targeting SMDCs in preclinical development and clinical trials.
BIOORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Emilio R. Mustafa, Santiago Cordisco Gonzalez, Marjorie Damian, Sonia Cantel, Severine Denoyelle, Renaud Wagner, Helgi B. Schioth, Jean-Alain Fehrentz, Jean-Louis Baneres, Mario Perello, Jesica Raingo
Summary: The study revealed that LEAP2 acts as an antagonist and inverse agonist of GHSR, preventing its interaction with receptors and modulating D2R signaling on Ca(V)2.2 currents.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maria Marti-Solano
Summary: Members of the G protein-coupled receptor (GPCR) family can sense a wide range of biomolecules and activate intracellular signalling cascades that regulate key aspects of cell physiology, making them the most successful drug target class so far. However, understanding the direct links between receptor activation and physiological outcomes is still a challenge. Recent studies using novel biosensors and high-throughput techniques have revealed how receptor function can be diversified in a spatial, temporal, or cell-specific manner, impacting our understanding of receptor function in health and disease, and aiding in the search for more selective and effective GPCR drug candidates.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Jessica Lu, Sarah J. Piper, Peishen Zhao, Laurence J. Miller, Denise Wootten, Patrick M. Sexton
Summary: Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides that play important roles in various physiological and pathological processes by activating specific receptors. The structural similarities between these peptides and their receptors present challenges in designing selective therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Edin Muratspahic, Bernhard Retzl, Leopold Duerrauer, Michael Freissmuth, Christian F. W. Becker, Christian W. Gruber
Summary: Peptides have shown promise in GPCR drug discovery, particularly in the field of analgesics. By genome mining, novel KOR peptide ligands derived from blenny fish have been identified, exhibiting high affinity and potency for KOR activation.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yiran Wu, Liting Zeng, Suwen Zhao
Summary: Adrenergic receptors, as G protein-coupled receptors for epinephrine and norepinephrine, are targeted by drugs for treating hypertension, hypotension, and asthma. Structural biology studies have provided insights into the molecular mechanisms of ligand recognition and receptor activation, as well as recent advances in structure-based ligand discovery against adrenergic receptors.
Article
Biochemistry & Molecular Biology
Lukas Zell, Constanze Lainer, Jakub Kollar, Veronika Temml, Daniela Schuster
Summary: Diseases of the central nervous system are becoming more prevalent globally. The current drugs targeting D2R suffer from adverse effects due to promiscuous receptor activity. This study combines in silico and in vitro approaches to identify novel D2R ligands, which could aid in developing new drug candidates for D2R-associated pathologies.
Article
Chemistry, Applied
Federica Valentini, Benedetta Di Erasmo, Carlo Ciancuti, Simone Rossi, Samuele Maramai, Maurizio Taddei, Luigi Vaccaro
Summary: In this study, lignin-derived phenolic compounds were converted into N-substituted cyclohexylamines via a cascade hydrogenation/reductive amination process. A tailor-made macroreticular POLITAG-20-Pd(0) heterogeneous catalytic system was developed, allowing the use of water as a safe reaction medium and minimizing the H-source employed. The catalyst showed a long durability and high efficiency, with the ability to be recycled for 20 consecutive runs and minimize waste associated with the work-up procedure.
Article
Chemistry, Applied
Nusrat Shafiq, Uzma Arshad, Simone Brogi, Maryam Rashid, Naila Rafiq, Shagufta Parveen
Summary: This study identifies stenocephol, a compound derived from the widely distributed plant Seriphidium stenocephalum, as a potential anti-diabetic and anti-cancer agent. It demonstrates inhibitory activity against glycogen phosphorylase and HepG2 cells and provides insights into its mechanism of action through computational investigation.
NATURAL PRODUCT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mohammad M. M. Al-Sanea, Abdelrahman Hamdi, Simone Brogi, Samar S. Tawfik, Dina I. A. Othman, Mahmoud Elshal, Hidayat Ur Rahman, Della G. T. Parambi, Rehab M. Elbargisy, Samy Selim, Ehab M. M. Mostafa, Ahmed A. B. Mohamed
Summary: A novel series of antipyrine derivatives containing 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, and pyrimidines were synthesized and evaluated as potential in vitro COX-2 inhibitors. Compounds 4b-d and 8d showed the highest potency, with a half-maximal inhibitory concentration range of 53-69 nM compared to Celecoxib. Compounds 4b and 4c were selected based on their COX-2 selectivity index for further investigation, including in vivo evaluation and molecular docking simulations.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Justyna Godyn, Paula Zareba, Dorota Stary, Maria Kaleta, Kamil J. Kuder, Gniewomir Latacz, Szczepan Mogilski, David Reiner-Link, Annika Frank, Agata Doroz-Plonka, Agnieszka Olejarz-Maciej, Sylwia Sudol-Talaj, Tobias Nolte, Jadwiga Handzlik, Holger Stark, Anna Wieckowska, Barbara Malawska, Katarzyna Kiec-Kononowicz, Dorota Lazewska, Marek Bajda
Summary: The study designed and synthesized a novel series of benzophenone derivatives. Among them, compound 6 showed high affinity for H3R and significant inhibitory activity towards BuChE. In vitro studies demonstrated that compound 6 had moderate metabolic stability and good permeability. In vivo activity tests revealed that compound 6 exhibited analgesic properties in acute and inflammatory pain.
Article
Cell Biology
Kerstin Griess, Michael Rieck, Nadine Muller, Gergely Karsai, Sonja Hartwig, Angela Pelligra, Robert Hardt, Caroline Schlegel, Jennifer Kuboth, Celina Uhlemeyer, Sandra Trenkamp, Kay Jeruschke, Jurgen Weiss, Leon Peifer-Weiss, Weiwei Xu, Sandra Cames, Xiaoyan Yi, Miriam Cnop, Mathias Beller, Holger Stark, Arun Kumar Kondadi, Andreas S. Reichert, Daniel Markgraf, Marianne Wammers, Dieter Haeussinger, Oliver Kuss, Stefan Lehr, Decio Eizirik, Heiko Lickert, Eckhard Lammert, Michael Roden, Dominic Winter, Hadi Al-Hasani, Doris Hoeglinger, Thorsten Hornemann, Jens C. Bruning, Bengt-Frederik Belgardt
Summary: Impaired proinsulin-to-insulin processing in pancreatic beta-cells is a key defective step in both type 1 diabetes and type 2 diabetes. This study reveals the roles of specific sphingolipid species and sphingolipid-binding proteins in beta-cell function and T2D-associated beta-cell failure.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Donia E. Hafez, Mariam Dubiel, Gabriella La Spada, Marco Catto, David Reiner-Link, Yu-Ting Syu, Mohammad Abdel-Halim, Tsong-Long Hwang, Holger Stark, Ashraf H. Abadi
Summary: Introduced a multi-targeted ligand for neurodegenerative diseases, such as Alzheimer's disease, which offers an improved therapeutic alternative compared to the traditional one-target, one-molecule approach. Certain compounds showed potential for multi-targeting by evaluating their interactions with AChE, BuChE, and MAO-B, suggesting their potential as lead structures for developing new multi-targeting anti-AD agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Khushbu Wadhwa, Hardeep Kaur, Neha Kapoor, Simone Brogi
Summary: Due to the limited availability of antifungal drugs and the emergence of drug-resistant strains, novel antifungal agents are urgently needed. The authors have developed a screening platform using computational and biological methods and identified sesamin as a potential antifungal agent. Sesamin showed promising results in inhibiting the growth of Candida species and exhibited synergistic effects with fluconazole.
Article
Chemistry, Medicinal
Alessandro Papa, Ilaria Cursaro, Luca Pozzetti, Chiara Contri, Martina Cappello, Silvia Pasquini, Gabriele Carullo, Anna Ramunno, Sandra Gemma, Katia Varani, Stefania Butini, Giuseppe Campiani, Fabrizio Vincenzi
Summary: This study aimed to develop multitarget inhibitors for the endocannabinoid system and epigenetic machinery to achieve synergistic therapeutic effects in oxidative stress-related conditions. The first-in-class FAAH-HDAC multitarget inhibitors were designed, synthesized, and evaluated for their neuroprotective properties. Compound 4h showed balanced inhibitory activity against the selected targets and outperformed the standard antioxidant in vitro.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Gabriele Carullo, Giovanni Di Bonaventura, Sara Rossi, Veronica Lupetti, Valeria Tudino, Simone Brogi, Stefania Butini, Giuseppe Campiani, Sandra Gemma, Arianna Pompilio
Summary: Pseudomonas aeruginosa is a pathogenic bacterium responsible for various infections in humans. Treating infections in cystic fibrosis patients is a global healthcare problem. Anti-virulence compounds have shown promise as adjuvant therapy for reducing the pathogenicity of Pseudomonas aeruginosa.
Editorial Material
Virology
Simone Brogi
Review
Biochemistry & Molecular Biology
Rita Tabanelli, Simone Brogi, Vincenzo Calderone
Summary: This review article discusses the potential use of opioids in treating various diseases and focuses on targeting opioid receptors for treating opioid use disorder, drug withdrawal, and addiction. However, the use of opioids is associated with numerous side effects. Therefore, the identification of opioid receptor ligands with fewer adverse effects is necessary. The article analyzes promising molecules for the treatment of opioid use disorder, including in vivo studies and clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Riccardo Fedeli, Ludovica Marotta, Luca Frattaruolo, Alice Panti, Gabriele Carullo, Fabio Fusi, Simona Saponara, Sandra Gemma, Stefania Butini, Anna Rita Cappello, Andrea Vannini, Giuseppe Campiani, Stefano Loppi
Summary: Wood distillate (WD) is a bio-based product that, when applied to the leaves, improves the quality and antioxidant profile of tomato fruits. Chemical and biological analysis revealed the presence of various fatty acids, amino acids, and sugars in WD-treated tomatoes. The extracts from these tomatoes showed promising anti-inflammatory effects in cells and slight vasorelaxant activity in rat aorta rings.
JOURNAL OF FOOD SCIENCE
(2023)