ArticleChemMedChem2019
A Small-Molecule SIRT2 Inhibitor That Promotes K-Ras4a Lysine Fatty-Acylation.
Article in ChemMedChem, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- From Pharmacophore to Warhead: NADAngewandte Chemie (International ed. in English) · 2025Article
- Sirtuin 1 and Sirtuin 2 Gene Expressions in Colorectal Cancers.Journal of clinical practice and research · 2025Article
- Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions.Journal of medicinal chemistry · 2025Article
- Rapid and high-throughput screening of proteolysis targeting chimeras using a dual-reporter system expressing fluorescence protein and luciferase.BMC biology · 2025Article
- Distribution and diversity of classical deacylases in bacteria.Nature communications · 2024Article
- Screening approach by a combination of computational and in vitro experiments: identification of fluvastatin sodium as a potential SIRT2 inhibitor.Journal of molecular modeling · 2024Article
- Sirt2 inhibition improves gut epithelial barrier integrity and protects mice from colitis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Current Trends in Sirtuin Activator and Inhibitor Development.Molecules (Basel, Switzerland) · 2024Review
- A homogeneous time-resolved fluorescence screen to identify SIRT2 deacetylase and defatty-acylase inhibitors.PloS one · 2024Article
- Continuous Fluorescent Sirtuin Activity Assay Based on Fatty Acylated Lysines.International journal of molecular sciences · 2023Article
- Continuous Histone Deacylase Activity Assays.Methods in molecular biology (Clifton, N.J.) · 2023Article
- SIRT2 plays complex roles in neuroinflammation neuroimmunology-associated disorders.Frontiers in immunology · 2023Review
- Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer.Biomolecules · 2022Review
- Virtual Screening in the Identification of Sirtuins' Activity Modulators.Molecules (Basel, Switzerland) · 2022Review
- Golgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation.Nature communications · 2022Article
- Development of a NanoBRET assay to validate inhibitors of Sirt2-mediated lysine deacetylation and defatty-acylation that block prostate cancer cell migration.RSC chemical biology · 2022Article
- Bioinformatic Analysis of the Effect of theBioMed research international · 2022Article
- Emerging role of SIRT2 in non-small cell lung cancer.Oncology letters · 2021Review
- A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications.Chemical reviews · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
SIRT2, a member of the sirtuin family of protein lysine deacylases, has been identified as a promising therapeutic target for treating cancer. In addition to catalyzing deacetylation, SIRT2 has recently been shown to remove fatty acyl groups from K-Ras4a and promote its transforming activity. Among the SIRT2-specific inhibitors, only the thiomyristoyl lysine compound TM can weakly inhibit the demyristoylation activity of SIRT2. Therefore, more potent small-molecule SIRT2 inhibitors are needed to further evaluate the therapeutic potential of SIRT2 inhibition, and to understand the function of protein lysine defatty-acylation. Herein we report a SIRT2 inhibitor, JH-T4, which can increase K-Ras4a lysine fatty acylation. This is the first small-molecule inhibitor that can modulate the lysine fatty acylation levels of K-Ras4a. JH-T4 also inhibits SIRT1 and SIRT3 in vitro. The increased potency of JH-T4 is likely due to the formation of hydrogen bonding between the hydroxy group and SIRT1, SIRT2, and SIRT3. This is further supported by in vitro studies with another small-molecule inhibitor, NH-TM. These studies provide useful insight for future SIRT2 inhibitor development.
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Registered trials
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