Article
Cell Biology
Christopher M. Brennan, Abby S. Hill, Michael St Andre, Xianfeng Li, Vijaya Madeti, Susanne Breitkopf, Seth Garren, Liang Xue, Tamara Gilbert, Angela Hadjipanayis, Mara Monetti, Charles P. Emerson Jr, Robert Moccia, Jane Owens, Nicolas Christoforou
Summary: This study investigated the kinetics of DUX4-induced stresses and found that the JNK and p38 MAP kinase pathways are activated in DUX4-mediated FSHD, providing further insights into potential therapeutic targets.
DISEASE MODELS & MECHANISMS
(2022)
Article
Chemistry, Medicinal
Esther Carrasco, Patricia Gomez-Gutierrez, Pedro M. Campos, Miguel Vega, Angel Messeguer, Juan J. Perez
Summary: A new orally available, potent and selective inhibitor of interleukin-1 beta has been discovered, showing promising results in reducing disease severity and efficacy in a mouse endotoxic shock model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Gordana Scepanovic, Miranda Victoria Hunter, Ran Kafri, Rodrigo Fernandez-Gonzalez
Summary: The research demonstrates that in Drosophila embryos, activation of p38 kinase helps limit wound size and promote rapid wound healing by increasing cell volume around the wound.
Article
Chemistry, Multidisciplinary
Linyao Zhao, Yixuan Wang, Yang Xu, Qian Sun, Hao Liu, Qianxue Chen, Baohui Liu
Summary: The study demonstrated that BIRB796 inhibits proliferation and invasion in GBM cells, suggesting its potential as an adjuvant therapy to enhance the efficacy of GBM treatment.
Article
Biology
Michal Otreba, Johanna Johansson Sjolander, Morten Grotli, Per Sunnerhagen
Summary: The small molecule INR119 enhances the activity of protein kinases in fission yeast and human cells under oxidative stress, with a potential conservation of its mechanism of action between yeast and humans.
Article
Biochemistry & Molecular Biology
Ganesan Senthil Kumar, Rebecca Page, Wolfgang Peti
Summary: The study revealed that the binding of p38 with MKK6 influences helix alpha F and engages not only through its hydrophobic docking groove; Unlike MAPK phosphatases, the p38 conserved docking (CD) site is minimally affected by MKK6 binding; These interactions with p38 are conserved independent of the MKK6 activation state, suggesting differences in specificity markers of p38 regulation by upstream kinases.
Article
Chemistry, Medicinal
Sandra Roehm, Benedict-Tilman Berger, Martin Schroeder, Deep Chatterjee, Sebastian Mathea, Andreas C. Joerger, Daniel M. Pinkas, Joshua C. Bufton, Amelie Tjaden, Lohitesh Kovooru, Mark Kudolo, Christian Pohl, Alex N. Bullock, Susanne Mueller, Stefan Laufer, Stefan Knapp
Summary: In this study, a potent and cell-active dual DDR/p38 chemical probe was developed, along with a structurally related negative control, for studying DDR kinase signaling. The structure-guided design approach provided insights into the folding process of p38 and how non-conserved amino acids modulate inhibitor selectivity. The developed DDR/p38 probe is a valuable tool for investigating the role of DDR kinase in normal physiology and disease development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Cell Biology
Begona Canovas, Angel R. Nebreda
Summary: The ability of cells to cope with various stressful situations is crucial for survival, with p38 alpha kinase playing a key role in the cellular stress response. Understanding the diversity of p38 alpha substrates, their mechanisms, and their connections to specific cellular functions is important for insights into physiology and pathology. Dysregulation of the p38 alpha pathway has been linked to diseases such as inflammation, immune disorders, and cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Enkhtuya Radnaa, Lauren Richardson, Brett Goldman, Jared K. Burks, Tuvshintugs Baljinnyam, Natasha Vora, Hui-Juan Zhang, Elizabeth A. Bonney, Arum Han, Ramkumar Menon
Summary: This study investigated the impact of oxidative stress on p38 MAPK signaling and cell fate, using amnion epithelial cells. The results showed that excessive activation of p38 can have adverse effects on cell behavior and tissue homeostasis.
Article
Biochemistry & Molecular Biology
Adam L. Poti, Laura Denes, Kinga Papp, Csaba Bato, Zoltan Banoczi, Attila Remenyi, Anita Alexa
Summary: Protein kinases are essential for cell signaling and have been targeted for therapeutic purposes for many years. Inhibiting kinase activity or interfering with kinase docking can be alternative strategies for controlling kinases. The development of phosphorylation-assisted luciferase complementation (PhALC) sensors allows for the quantitative analysis of kinase activity or kinase docking, making it a useful tool in research and high-throughput screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Psychiatry
Ali S. Imami, Robert E. McCullumsmith, Sinead M. O'Donovan
Summary: Drug repurposing is an invaluable strategy for identifying new uses for existing drug therapies, especially in terms of time and financial costs compared to novel drug development. The COVID-19 pandemic has led to a surge in the use of bioinformatic tools to identify repurposable drugs, with applications extending to treatments for CNS disorders. These advancements in bioinformatic drug repurposing offer promise for improved treatments for complex brain disorders such as neuropsychiatric and neurological disorders.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Juan R. Perea, Esther Garcia, Laura Valles-Saiz, Raquel Cuadros, Felix Hernandez, Marta Bolos, Jesus Avila
Summary: Tauopathies are neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein. Inflammation, particularly the activation of microglia, is also involved in these diseases. The p38 MAPK pathway, primarily expressed in glia, has been associated with tau phosphorylation in neurodegenerative diseases like Alzheimer's Disease. Using a mouse model, researchers found increased p38 activation in microglia of the hippocampus during aging. Interestingly, these mice also displayed activated rod microglia, although p38 activation was decreased in this subpopulation. This suggests that rod microglia may have a neuroprotective phenotype in the context of tau pathology.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Laercia K. D. Paiva Ferreira, Larissa A. M. Paiva Ferreira, Grasiela C. Bezerra Barros, Talissa Mozzini Monteiro, Luiz A. de Araujo Silva, Ramon de A. Pereira, Pedro T. R. Figueiredo, Adriano Francisco Alves, Luis Cezar Rodrigues, Marcia Regina Piuvezam
Summary: MHTP shows therapeutic effects in the experimental model of CARAS, including reducing symptoms, inhibiting eosinophil migration, decreasing tissue inflammation, and regulating immune cytokines. These effects are mediated through the p38/ERK1/2 MAP kinase signaling pathway axis and the shutdown of intracellular transduction signals underlying cytokine gene transcription.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Applied
Michael Forster, Heike K. Wentsch-Teltschik, Stefan A. Laufer
Summary: The p38 alpha MAP kinase has been extensively studied, leading to the successful development of dibenzosuberone-based inhibitors such as skepinone-L. Optimization of the synthetic route resulted in improved overall yield, elimination of chromatographic purification, and successful scale-up of the production process, ensuring a stable supply for further development.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Biology
Pablo Bora, Lenka Gahurova, Tomas Masek, Andrea Hauserova, David Potesil, Denisa Jansova, Andrej Susor, Zbynek Zdrahal, Anna Ajduk, Martin Pospisek, Alexander W. Bruce
Summary: Bora et al. demonstrate that p38-MAPK activity in the early blastocyst stage regulates ribosome-related gene expression, rRNA processing, polysome formation, and protein translation, suggesting a specific role for p38-MAPKs in facilitating translational environment during mouse blastocyst primitive endoderm differentiation.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)