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An mTOR inhibitor discovery system using drug-sensitized yeast.
Geroscience
January 2025
Department of Biomedical Sciences, Western University of Health Sciences, Lebanon, OR, 97355, USA.
Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered in Saccharomyces cerevisiae (yeast) which contains two TOR paralogs, TOR1 and TOR2.
View Article and Find Full Text PDFGenome-wide identification of carboxyesterase family members reveals the function of GeCXE9 in the catabolism of parishin A in Gastrodia elata.
Plant Cell Rep
January 2025
Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.
GeCXE9 can catalyze the hydrolysis of parishin A via two pathways during the medicinal processing of Gastrodia elata. Gastrodia elata Bl. is used in traditional Chinese medicine for its bioactive compounds, particularly phenols.
View Article and Find Full Text PDFDiscovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFTransformation of Distinct Superatoms to Superalkalis by Successive Ligation of Thymine Nucleobases.
J Phys Chem A
January 2025
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350108, People's Republic of China.
The ligation strategy has been widely used in the chemical synthesis of atomically precise clusters. A series of thymine (T)-ligated Al-T ( = Be, Al, C; = 1-5) complexes have been studied to reveal the effect of DNA nucleobase ligands on the electronic structures of different superatoms in the present work. In addition to its protective role, the successive attachment of thymine ligands significantly lowers the adiabatic ionization energies (AIEs) of the studied Al superatoms with filled and unfilled electronic shells.
View Article and Find Full Text PDFA comparative life cycle analysis of Sol-Char and anaerobic digestion sanitation systems.
Sci Total Environ
January 2025
Leiden University, Institute of Environmental Science - Industrial Ecology, Van Steenisgebouw, Einsteinweg 2, 2333 CC Leiden, the Netherlands. Electronic address:
In this study, we compared the Sol-Char sanitation system with an Anaerobic Digestion (AD) system using Life Cycle Assessment (LCA) to evaluate their environmental impacts. Since both systems offer opportunities for human waste treatment and resource recovery, understanding their performance is crucial. This comparison aims to determine their environmental impacts while considering diverse factors, such as energy production and nutrient recovery.
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