Article
Chemistry, Medicinal
Huikai Sun, Holger Monenschein, Hans H. Schiffer, Holly A. Reichard, Shota Kikuchi, Maria Hopkins, Todd K. Macklin, Stephen Hitchcock, Mark Adams, Jason Green, Jason Brown, Sean T. Murphy, Nidhi Kaushal, Deanna R. Collia, Steve Moore, William J. Ray, Nicole Marion English, Mark Beresford Lewis Carlton, Nicola L. Brice
Summary: Parkinson's disease is a chronic and progressive movement disorder with an urgent need for efficient symptomatic therapies. GPR6 inverse agonists have shown potential in reversing symptoms and improving mobility, with the clinical compound CVN424 currently in development for the treatment of motor symptoms in Parkinson's disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Remy A. Yovanno, Tsung Han Chou, Sarah J. Brantley, Hiro Furukawa, Albert Y. Lau
Summary: This study investigated the mechanisms of D-serine in receptor activation and found that D-serine competes with glutamate for binding to GluN2A. The inhibitory effect of D-serine at high concentrations was confirmed through electrophysiology experiments.
Article
Pharmacology & Pharmacy
Sarina Gadgaard, Wijnand J. C. van der Velden, Sine P. Schiellerup, Jenna Elizabeth Hunt, Maria B. N. Gabe, Johanne Agerlin Windelov, Geke Aline Boer, Hannelouise Kissow, Cathrine Orskov, Jens J. Holst, Bolette Hartmann, Mette M. Rosenkilde
Summary: By studying the structure and functional characteristics of two radioligands, we found that subepithelial myofibroblasts are the main site of GLP-2 receptor expression.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biophysics
Jiansen Li, Wenli Wang, Jing Liu, He Li, Ninglong Zhang, Fengzhen Yang, Haowei Dong, Xia Sun, Gaole Chen, Yuxia Fan, Yemin Guo, Yuan Liu
Summary: In this study, an electrochemical biosensor based on a double-signal amplification strategy was constructed using single-walled carbon nanotubes (SWCNTs) and Prussian blue (PB), to successfully quantify the umami taste of four representative substances. The biosensor showed high sensitivity and selectivity in detecting umami substances with a normalized signal intensity of over 90%.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Chemistry, Analytical
Thierry N. J. Fouquet, Jean-Arthur Amalian, Nathan Aniel, Isaure Carvin-Sergent, Sebastien Issa, Salome Poyer, Delphine Crozet, Pierre Giusti, Didier Gigmes, Thomas Trimaille, Laurence Charles
Summary: Mass spectrometry has become an essential tool in studying the degradation behavior of polyesters due to its speed and sensitivity. By using reactive desorption electrospray ionization, online monitoring of chain solvolysis during the degradation process was achieved. Analysis showed that the susceptibility of ester bonds to solvolysis is higher in glycolic acid than in lactic acid. This method offers perspectives for evaluating the intrinsic degradability of different polyesters and determining the degradability of polymers known to degrade via erosion.
ANALYTICAL CHEMISTRY
(2021)
Article
Immunology
Shumin Yue, Tian Wang, Yunqi Yang, Yiqian Fan, Lin Zhou, Mingan Li, Fenghua Fu
Summary: The study found that dopamine and dopamine receptor agonists are associated with inflammation and immune response. The dopamine receptor agonist RoMS can protect against acute liver injury induced by LPS/D-Gal in mice by regulating the NF-kappa B inflammatory signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
David A. Griffith, David J. Edmonds, Jean-Philippe Fortin, Amit S. Kalgutkar, J. Brent Kuzmiski, Paula M. Loria, Aditi R. Saxena, Scott W. Bagley, Clare Buckeridge, John M. Curto, David R. Derksen, Joao M. Dias, Matthew C. Griffor, Seungil Han, V. Margaret Jackson, Margaret S. Landis, Daniel Lettiere, Chris Limberakis, Yuhang Liu, Alan M. Mathiowetz, Jayesh C. Patel, David W. Piotrowski, David A. Price, Roger B. Ruggeri, David A. Tess
Summary: Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have been a breakthrough in diabetes therapy, but their use is limited due to the need for injection. In this study, a small-molecule GLP-1R agonist, danuglipron, was discovered that can be taken orally. Danuglipron showed the ability to promote GLP-1R signaling and increase insulin levels in primates, but not in rodents. This discovery opens up the possibility of oral small-molecule therapies targeting the validated GLP-1R for metabolic health.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Khanh Dinh Quoc Nguyen, Michael Vigers, Eric Sefah, Susanna Seppala, Jennifer Paige Hoover, Nicole Star Schonenbach, Blake Mertz, Michelle Ann O'Malley, Songi Han
Summary: The intrinsically disordered C-terminus of the human adenosine A(2A) receptor (A(2A)R) is found to be a prominent driving factor for receptor homo-oligomerization. A(2A)R oligomer formation decreases progressively with the shortening of the C-terminus, with multiple interaction types contributing to the oligomerization, including disulfide linkages, hydrogen bonds, electrostatic interactions, and hydrophobic interactions. These interactions are enhanced by depletion interactions, creating a tunable network of bonds for A(2A)R oligomers to adopt multiple interfaces.
Article
Chemistry, Medicinal
Li Lin, Yongmin Liu, Li Chen, Yue Dai, Yufeng Xia
Summary: Researchers designed and synthesized a compound III11 that can activate AhR, which showed good bioavailability and remarkable therapeutic effects in treating inflammatory diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Rosalba Mansi, Pascale Plas, Georges Vauquelin, Melpomeni Fani
Summary: Comparing the binding kinetics and cellular mechanisms of [Lu-177]Lu-OPS201 and [Lu-177]Lu-DOTA-TATE, the study found that [Lu-177]Lu-OPS201 recognized more receptor binding sites, with faster association and slower dissociation, explaining the improved therapeutic efficacy of [Lu-177]Lu-OPS201 compared to [Lu-177]Lu-DOTA-TATE.
Article
Chemistry, Medicinal
Tasia Amelia, Jacobus P. D. van Veldhoven, Matteo Falsini, Rongfang Liu, Laura H. Heitman, Gerard J. P. van Westen, Elena Segala, Gregory Verdon, Robert K. Y. Cheng, Robert M. Cooke, Daan van der Es, Adriaan P. IJzerman
Summary: In this study, the crystal structure of an engineered human adenosine A(2A) receptor bound to a partial agonist was determined and compared to structures bound to a full agonist or antagonist/inverse agonist. Interaction between the partial agonist and amino acids in the ligand binding pocket led to the development of a library of derivatives with varied activities. Some derivatives showed partial agonist properties while others acted as inverse agonists, with additional computational docking studies providing insights into this behavior.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Susanne Prokop, Peter Abranyi-Balogh, Benjamin Barti, Marton Vamosi, Miklos Zoldi, Laszlo Barna, Gabriella M. Urban, Andras David Toth, Barna Dudok, Attila Egyed, Hui Deng, Gian Marco Leggio, Laszlo Hunyady, Mario van der Stelt, Gyorgy M. Keseru, Istvan Katona
Summary: The PharmacoSTORM single-molecule imaging technique combines fluorescent ligands and immunolabeling to provide a new approach for molecular pharmacology research at the cellular and subcellular levels, enabling precise quantification of drug-target interactions. By studying cariprazine binding to D3 dopamine receptors, the technique allows for accurate measurement of drug-target interactions and sheds light on its neurobiological substrate.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Cyrielle Billon, Sadichha Sitaula, Subhashis Banerjee, Ryan Welch, Bahaa Elgendy, Lamees Hegazy, Tae Gyu Oh, Melissa Kazantzis, Arindam Chatterjee, John Chrivia, Matthew E. Hayes, Weiyi Xu, Angelica Hamilton, Janice M. Huss, Lilei Zhang, John K. Walker, Michael Downes, Ronald M. Evans, Thomas P. Burris
Summary: Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that ERRs play an important role in skeletal muscle exercise capacity. Here, we report the identification of a synthetic ERR pan agonist, SLU-PP-332, that targets all three ERRs but has the highest potency for ERR alpha. SLU-PP-332 increases mitochondrial function and cellular respiration, and enhances exercise endurance.
ACS CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hyun-Kyu Choi, Peiwen Cong, Chenghao Ge, Aswin Natarajan, Baoyu Liu, Yong Zhang, Kaitao Li, Muaz Nik Rushdi, Wei Chen, Jizhong Lou, Michelle Krogsgaard, Cheng Zhu
Summary: Catch bonds form when T cell receptors (TCR) interact with agonist peptide-MHC (pMHC) complexes, with the lifetime of the bond increasing with applied force. In this study, the authors develop two models and analyze 55 datasets to quantitatively integrate and classify different bond behaviors and biological activities. The models can distinguish class I from class II MHCs and correlate their structural parameters with TCR/pMHC potency to trigger T cell activation, providing insights into the mechanisms of TCR mechanosensing.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Andrea Ramos de Castro Moreira, Ericka Trarbach, Cristina Bellotti Formiga Bueno, Anna Louise Stellfeld Monteiro, Isabella Pacetti Pajaro Grande, Mario Padula, Gustavo Arantes Rosa Maciel, Andrea Glezer
Summary: In this study, six PRL-R variants associated with prolactinomas were identified, with two variants showing higher frequency in patients compared to the genomic database. These variants were associated with male sex, higher serum PRL levels, larger tumors, and cabergoline resistance. These findings suggest the involvement of the prolactin/prolactin receptor system in prolactinoma tumorigenesis and resistance to cabergoline.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)