A class of transmembrane proteins helps shuttle large drugs across the cell membrane.
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http://dx.doi.org/10.1126/science.adf4412 | DOI Listing |
Eur J Med Chem
January 2025
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin, 541004, China; National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Institute of Green Chemistry and Process Enhancement Technology, Huaiyin Institute of Technology, Huai'an, 223003, China. Electronic address:
Nowadays, hybrid molecule with dual targets activity or effect is regarded as an effective strategy for combating the drug resistance development in cancer therapy. Herein, novel of bifunctional conjugates targeting tubulin and MMPs inhibitors were synthesized. Among them, 15j exhibited robust anticancer activity in vitro and in vivo, with IC values of 0.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
The bifunctional mechanism, involving multiactive compositions to simultaneously dissociate water molecules and optimize intermediate adsorption, has been widely used in the design of catalysts to boost water electrolysis for sustainable hydrogen energy production but remains debatable due to difficulties in accurately identifying the reaction process. Here, we proposed the concept of well-defined Lewis pairs in single-atom catalysts, with a unique acid-base nature, to comprehensively understand the exact role of multiactive compositions in an alkaline hydrogen evolution reaction. By facilely adjusting active moieties, the induced synergistic effect between Lewis pairs (M-P/S/Cr pairs, M = Ru, Ir, Pt) can significantly facilitate the cleavage of the H-OH bond and accelerate the removal of intermediates, thereby switching the rate-determining step from the Volmer step to the Heyrovsky step.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States.
Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering a method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" proteins. This concept, pioneered by Crews and his team, introduced the use of small molecules to link a target protein to an E3 ubiquitin ligase, inducing ubiquitination and subsequent degradation of the target protein.
View Article and Find Full Text PDFRSC Med Chem
December 2024
Department of Pharmaceutical Sciences, Guru Nanak Dev University Amritsar Punjab 143005 India
Considering the multifactorial and complex nature of Alzheimer's disease and the requirement of an optimum multifunctional anti-Alzheimer's agent, a series of triazole tethered coumarin-eugenol hybrid molecules was designed as potential multifunctional anti-Alzheimer's agents using donepezil and a template. The designed hybrid molecules were synthesized a click chemistry approach and preliminarily screened for cholinesterase and Aβ aggregation inhibition. Among them, AS15 emerged as a selective inhibitor of AChE (IC = 0.
View Article and Find Full Text PDFNature
January 2025
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
C-H activation is the most direct way of functionalizing organic molecules. Many advances in this field still require specific directing groups to achieve the necessary activity and selectivity. Developing C-H activation reactions directed by native functional groups is essential for their broad application in synthesis.
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