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Abstract Late‐stage functionalization (LSF) of drug molecules is an approach to generate modified molecules that retain functional groups present in the active drugs. Here, we report a study that seeks to characterize the potential value of high‐throughput desorption electrospray ionization mass spectrometry (HT DESI‐MS) for small‐scale rapid LSF. In conventional route screening, HT‐based DESI‐MS provides contactless, rapid analysis, reliable and reproducible data, minimal sample requirement, and exceptional tolerance to high salt concentrations. Ezetimibe (E), an established hypertension drug, is targeted for modification by LSF. C−H alkenylation and azo‐click reactions are utilized to explore this approach to synthesis and analytical characterization. The effect of choice of reactant, stoichiometry, catalyst, and solvent are studied for both reactions using high throughput DESI‐MS experiments. Optimum conditions for the formation of LSF products are established with identification by tandem mass spectrometry (MS/MS).
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This content will become publicly available on January 24, 2026
Mathematical Characterization of Drug-Induced Persistence in Cancer
Abstract We introduce a general phenomenological framework for understanding how phenotypic plasticity gives rise to drug persisters. These persisters, often quiescent but sometimes which again return to cycling, survive in the presence of treatment and eventually can lead to mutants with true resistance. Our framework builds on recent experimental observations regarding variations between and among single-cell clones and the possible role of the drug itself in enhancing the survival strategy. Predictions of our approach include the existence of an optimum drug concentration as well as an optimum drug holiday schedule to minimize the persistence-based threat.
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- Award ID(s):
- 2019745
- PAR ID:
- 10597040
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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