ArticleJournal of medicinal chemistry2017
Thienopyrimidinone Based Sirtuin-2 (SIRT2)-Selective Inhibitors Bind in the Ligand Induced Selectivity Pocket.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed.
- Probing pyrazolo-pyrimidines as SIRT2 inhibitorsRSC medicinal chemistry · 2026Article
- Repurposing DrugBank compounds as NAD-dependent deacetylase sirtuin 2 inhibitors via QSAR modelling with gradient boosting algorithms and all-atom molecular simulations.Molecular diversity · 2026Article
- Synergistic inhibition of metastatic melanoma by carvacrol and chloroquine: an in vitro and in silico investigation of apoptosis and molecular targets.Medical oncology (Northwood, London, England) · 2026Article
- From Pharmacophore to Warhead: NADAngewandte Chemie (International ed. in English) · 2025Article
- Sirtuins as Therapeutic Targets for Treating Cancer, Metabolic Diseases, and Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Discovery of novel SIRT2 inhibitors with anti-NSCLC activity through multi-virtual screening and biological evaluation.Future medicinal chemistry · 2025Article
- Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions.Journal of medicinal chemistry · 2025Article
- Article
- Multicomponent reactions (MCRs) yielding medicinally relevant rings: a recent update and chemical space analysis of the scaffolds.RSC advances · 2025Review
- Discovery of Novel Thiazole-Based SIRT2 Inhibitors as Anticancer Agents: Molecular Modeling, Chemical Synthesis and Biological Assays.International journal of molecular sciences · 2024Article
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Computational Design and Optimization of Peptide Inhibitors for SIRT2.Pharmaceuticals (Basel, Switzerland) · 2024Article
- 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
- 5-((3-Amidobenzyl)oxy)nicotinamides as SIRT2 Inhibitors: A Study of Constrained Analogs.Molecules (Basel, Switzerland) · 2023Article
- Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.Journal of medicinal chemistry · 2023Article
- Novel Thiazole-Based SIRT2 Inhibitors Discovered via Molecular Modelling Studies and Enzymatic Assays.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Microtubule acetylation dyshomeostasis in Parkinson's disease.Translational neurodegeneration · 2023Review
- The Role of Histone Deacetylases in Acute Lung Injury-Friend or Foe.International journal of molecular sciences · 2023Review
- The roles of sirtuins in ferroptosis.Frontiers in physiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity. Importantly, we report a cocrystal structure of one of our compounds (29c) bound to SIRT2. This reveals our series to induce the formation of a previously reported selectivity pocket but to bind in an inverted fashion to what might be intuitively expected. We believe these findings will contribute significantly to an understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, second generation inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.