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A Small Molecule That Inhibits OGT Activity in Cells
Open accessAbstract
O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. The biology of O-GlcNAc modification is still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. Here, we report a small molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. The development of this molecule validates high-throughput screening approaches for the discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models.
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Metadata
- Authors
- Ortiz-Meoz, R. F., Jiang, J., Lazarus, M. B., Orman, M., Janetzko, J., Fan, C., Duveau, D. Y., Tan, Z.-W., Thomas, C. J., & Walker, S.
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-03-18
- Volume
- 10
- Issue
- 6
- Pages
- 1392-1397
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- OpenAlex
- W2080462728
- Cited by
- 294
- References
- 56
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- green
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