ArticleACS chemical biology2019
A Glycoconjugated SIRT2 Inhibitor with Aqueous Solubility Allows Structure-Based Design of SIRT2 Inhibitors.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- A High-throughput Fluorescence Polarization Assay for Screening Sirtuin Inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Comparative Analysis of Biochemical and Cellular Assay Conditions and the Need for a Buffer That Mimics Cytoplasmic Environments.Molecules (Basel, Switzerland) · 2025Review
- Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- 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
- SIRT2 transgenic over-expression does not impact lifespan in mice.Aging cell · 2023Article
- Structure, functions, and recent advances in the development of SIRT2 inhibitors.Pharmaceutical science advances · 2023Review
- 5-((3-Amidobenzyl)oxy)nicotinamides as SIRT2 Inhibitors: A Study of Constrained Analogs.Molecules (Basel, Switzerland) · 2023Article
- Drug repurposing for ligand-induced rearrangement of Sirt2 active site-based inhibitors via molecular modeling and quantum mechanics calculations.Scientific reports · 2021Article
- Mechanism-based inhibitors of SIRT2: structure-activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration.RSC chemical biology · 2021Article
- Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function.Frontiers in cell and developmental biology · 2021Review
- Simultaneous Inhibition of SIRT2 Deacetylase and Defatty-Acylase Activities via a PROTAC Strategy.ACS medicinal chemistry letters · 2020Article
- Substrate-Dependent Modulation of SIRT2 by a Fluorescent Probe, 1-Aminoanthracene.Biochemistry · 2020Article
- NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle.Nature communications · 2020Article
- SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases.Frontiers in pharmacology · 2020Review
- Discovering Anti-Cancer DrugsFrontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Small molecule inhibitors for SIRT2, a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent protein lysine deacylases, have shown promise in treating cancer and neurodegenerative diseases. Developing SIRT2-selective inhibitors with better pharmacological properties is key to further realize the therapeutic potential of targeting SIRT2. One of the best SIRT2-selective inhibitors reported is a thiomyristoyl lysine compound called TM, which showed promising anticancer activity in mouse models without much toxicity to normal cells. The main limitations of TM, however, are the low aqueous solubility and lack of X-ray crystal structures to aid future drug design. Here, we designed and synthesized a glucose-conjugated TM (glucose-TM) analog with superior aqueous solubility. Although glucose-TM is not cell permeable, the excellent aqueous solubility allowed us to obtain a crystal structure of SIRT2 in complex with it. The structure enabled us to design several new TM analogs, one of which, NH4-6, showed superior water solubility and better anticancer activity in cell culture. The results of these studies provided important insights that will further fuel the future development of improved SIRT2 inhibitors as promising therapeutics for treating cancer and neurodegeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.