Genetic defects in telomere maintenance result in stem cell exhaustion and a spectrum of telomere biology diseases. Systemic treatments beyond organ transplantation are lacking for these diseases. Nagpal and colleagues identified small molecules that restore telomere maintenance in patient-derived stem cells, offering a promising therapy for telomere biology diseases.
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http://dx.doi.org/10.1016/j.tips.2020.05.003 | DOI Listing |
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
The Ca/calmodulin-dependent protein kinase II α (CaMKIIα) plays a crucial role in regulating neuronal signaling and higher brain functions, being involved in various brain diseases. Utilization of small molecules targeting the CaMKIIα hub domain has proved to be a promising strategy for specific CaMKIIα modulation and future therapy. Through an structure-based virtual screening campaign, we herein identified 2-arylthiazole-4-carboxylic acids as a new class of high-affinity CaMKIIα hub ligands.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Natural small molecule compounds play crucial roles in regulating fat deposition. Beta-sitosterol exhibits multiple biological activities such as cholesterol reduction and anticancer effects. However, its regulatory mechanism in the differentiation of bovine preadipocytes remains unclear.
View Article and Find Full Text PDFNanomicro Lett
January 2025
Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Institute of New Energy, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Fudan University, Shanghai, 200433, People's Republic of China.
Practical Zn metal batteries have been hindered by several challenges, including Zn dendrite growth, undesirable side reactions, and unstable electrode/electrolyte interface. These issues are particularly more serious in low-concentration electrolytes. Herein, we design a Zn salt-mediated electrolyte with in situ ring-opening polymerization of the small molecule organic solvent.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemical and Systems Biology, Stanford Cancer Institute, School of Medicine Stanford University, Stanford, California 94305-6104, United States.
Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.
View Article and Find Full Text PDFJ Virol
January 2025
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, Texas, USA.
Unlabelled: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein.
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