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- W2891673054 endingPage "1455.e14" @default.
- W2891673054 startingPage "1443" @default.
- W2891673054 abstract "The persistence of a pool of latently HIV-1-infected cells despite combination anti-retroviral therapy treatment is the major roadblock for a cure. The BAF (mammalian SWI/SNF) chromatin remodeling complex is involved in establishing and maintaining viral latency, making it an attractive drug target for HIV-1 latency reversal. Here we report a high-throughput screen for inhibitors of BAF-mediated transcription in cells and the subsequent identification of a 12-membered macrolactam. This compound binds ARID1A-specific BAF complexes, prevents nucleosomal positioning, and relieves transcriptional repression of HIV-1. Through this mechanism, these compounds are able to reverse HIV-1 latency in an in vitro T cell line, an ex vivo primary cell model of HIV-1 latency, and in patient CD4+ T cells without toxicity or T cell activation. These macrolactams represent a class of latency reversal agents with unique mechanism of action, and can be combined with other latency reversal agents to improve reservoir targeting." @default.
- W2891673054 created "2018-09-27" @default.
- W2891673054 creator A5002888060 @default.
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- W2891673054 creator A5082076463 @default.
- W2891673054 creator A5088044719 @default.
- W2891673054 creator A5091892696 @default.
- W2891673054 date "2018-12-01" @default.
- W2891673054 modified "2023-10-16" @default.
- W2891673054 title "Small Molecule Targeting of Specific BAF (mSWI/SNF) Complexes for HIV Latency Reversal" @default.
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