Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing?
Why is it relevant to propose epigenetic “Nutricures” to prevent diseases linked with ageing?
Repair of methyl lesions in RNA by oxidative demethylation
Nucleic acid methylation is one of the most important epigenetic modifications that have been studied intensively for the past several decades.
Discovery of an orally active subtype-selective HDAC inhibitor, chidamide, as an epigenetic modulator for cancer treatment
Tumorigenesis is maintained through a complex interplay of multiple cellular biological processes and is regulated to some extent by epigenetic control of gene expression.
Structural biology and chemistry of protein arginine methyltransferases
PRMT inhibitors can compete with cofactor, substrate, or bind at allosteric sites found in the active or inactive states.
Structure–activity relationship studies of SETD8 inhibitors
Comprehensive SAR studies of the first substrate-competitive SETD8 inhibitor led to the discovery of interesting SAR trends and novel analogs.
Design, synthesis, and preliminary bioactivity studies of substituted purine hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors
Histone deacetylase (HDAC) is a clinically validated target for anti-tumor therapy. In order to increase HDAC inhibition and efficiency, we developed a series of novel substituted purine hydroxamic acids as potent HDAC inhibitors.
Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor
Compound 35 is a potent and selective triazolopyridine inhibitor of the lysine demethylase KDM2A (pIC50 7.2).
Design and chemoproteomic functional characterization of a chemical probe targeted to bromodomains of BET family proteins
Selectivity of a PFI-1 based BET bromodomain probe was demonstrated using affinity capture in nuclear extracts from human cells.
Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors
With the aim of discovering novel G9a inhibitory chemotypes, we have identified a new quinoline inhibitor scaffold and better defined the pharmacophoric features of the central heterocycle.
3,5-Diamino-1,2,4-triazoles as a novel scaffold for potent, reversible LSD1 (KDM1A) inhibitors
Compounds 6 and 7 represent the first reversible LSD1 inhibitors with minimal cytotoxicity in vitro.
An azumamide C analogue without the zinc-binding functionality
Histone deacetylase (HDAC) inhibitors have attracted considerable attention due to their promise as therapeutic agents.
Pyrido- and benzisothiazolones as inhibitors of histone acetyltransferases (HATs)
We present structure–activity studies on pyrido- and benzisothiazolones as histone acetyltransferase (HAT) inhibitors. Distinct subtype-selectivity profiles were obtained in vitro that correlate with cytotoxicity profiles on cancer cells.
Structure-based approaches towards identification of fragments for the low-druggability ATAD2 bromodomain
Fragments for the development of ATAD2 bromodomain inhibitors have been identified and characterized by NMR and co-crystallization.
Evaluation of functional groups as acetyl-lysine mimetics for BET bromodomain inhibition
This work provides new insights into a range of acetyl-lysine mimetics as BET bromodomain inhibitors.
Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors
A HDAC, kinase inhibitor hybrid, (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide, 6, showed impressive anticancer action in a number of biochemical and cell-based assays.
About this collection
A MedChemComm themed issue guest edited by Dr Mark Bunnage and Professor James E. Bradner highlighting some of the latest exciting research from across the breadth of epigenetics research.
New articles will be added to this collection as they are published.