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- W3158053024 abstract "Activation-induced deaminase (AID) not only mutates DNA within the immunoglobulin loci to generate antibody diversity, but it also promotes development of B cell lymphomas. To tame this mutagen, we performed a quantitative high-throughput screen of over 90 000 compounds to see if AID activity could be mitigated. The enzymatic activity was assessed in biochemical assays to detect cytosine deamination and in cellular assays to measure class switch recombination. Three compounds showed promise via inhibition of switching in a transformed B cell line and in murine splenic B cells. These compounds have similar chemical structures, which suggests a shared mechanism of action. Importantly, the inhibitors blocked AID, but not a related cytosine DNA deaminase, APOBEC3B. We further determined that AID was continually expressed for several days after B cell activation to induce switching. This first report of small molecules that inhibit AID can be used to gain regulatory control over base editors." @default.
- W3158053024 created "2021-05-10" @default.
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- W3158053024 date "2021-05-07" @default.
- W3158053024 modified "2023-10-01" @default.
- W3158053024 title "Small Molecule Inhibitors of Activation-Induced Deaminase Decrease Class Switch Recombination in B Cells" @default.
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- W3158053024 doi "https://doi.org/10.1021/acsptsci.1c00064" @default.
- W3158053024 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8205235" @default.
- W3158053024 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34151211" @default.
- W3158053024 hasPublicationYear "2021" @default.
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