Disruption of c-Myc/Max heterodimerization induced by a novel anticancer agent endowed with 1,3-diphenylurea moiety: an in silico, chemoproteomics-based, and in vitro combined approach.

The intrinsically disordered protein (IDP) c-Myc plays a crucial role in regulating cell growth, proliferation, and apoptosis, making it a significant target for cancer therapy. Herein, we report an integrated approach combining computational and biological methods to uncover key c-Myc structural aspects aimed at identifying modulators of this protein. A virtual screening campaign starting from commercially available libraries was performed, leading to the selection of 11 promising c-Myc binders.

Epigenetic editing and epi-drugs: a combination strategy to simultaneously target KDM4 as a novel anticancer approach.

KDM4-A/B/C, preferentially demethylating di- and tri-methylated lysine 9 on histone H3, are overexpressed in cancers and considered interesting therapeutic targets. Consequently, KDM4 inhibitors have been developed to block their enzymatic activity. However, the potential lack of specificity of such small molecules (epi-drugs) may contribute to dose-limiting toxicities.

"Aging and epigenetic implications in radiotherapy: The promise of BNCT".

Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment.

Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9.

PROteolysis Targeting Chimera (PROTAC) technology is an innovative and potent approach for achieving targeted protein degradation (TPD). Within bromodomain-containing proteins, various degraders targeting BET family-related targets, for example, BRD4, were developed in the last years. On the other hand, a limited number of PROTACs acting against non-BET proteins were reported so far.

From Bench to Bedside: Translational Approaches to Cardiotoxicity in Breast Cancer, Lung Cancer, and Lymphoma Therapies.

Cardiotoxicity represents a critical challenge in cancer therapy, particularly in the treatment of thoracic tumors, such as lung cancer and lymphomas, as well as breast cancer. These malignancies stand out for their high prevalence and the widespread use of cardiotoxic treatments, such as chemotherapy, radiotherapy, and immunotherapy. This work underscores the importance of preclinical models in uncovering the mechanisms of cardiotoxicity and developing targeted prevention and mitigation strategies.

Unravelling the impact of the chromobox proteins in human cancers.

Chromobox (CBX) proteins play a crucial role in regulating epigenetic processes. They are extensively involved in various biological processes, including embryonic development, stem cell maintenance, cell proliferation and apoptosis control. The disruption and malfunction of CBXs in cancer typically results in the interference or abnormal activation of developmental pathways, which facilitate the onset, growth, and advancement of cancer.

Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential.

Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of , EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs.

Exploring the Role of CBX3 as a Potential Therapeutic Target in Lung Cancer.

Epigenetic changes regulate gene expression through histone modifications, chromatin remodeling, and protein translation of these modifications. The PRC1 and PRC2 complexes shape gene repression via histone modifications. Specifically, the CBX protein family aids PRC1 recruitment to chromatin, impacting the progressive multistep process driving chromatin silencing.

Correction to "Novel Antiproliferative Chimeric Compounds with Marked Histone Deacetylase Inhibitory Activity".

[This corrects the article DOI: 10.1021/ml5000959.].

Health-Promoting Effects, Phytochemical Constituents and Molecular Genetic Profile of the Purple Carrot 'Purple Sun' ( L.).

The purple carrot cultivar 'Purple Sun' ( L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time.

Therapeutic Potential of Natural Compounds Acting through Epigenetic Mechanisms in Cardiovascular Diseases: Current Findings and Future Directions.

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD.

The mA-independent role of epitranscriptomic factors in cancer.

Protein function alteration and protein mislocalization are cancer hallmarks that drive oncogenesis. N-methyladenosine (mA) deposition mediated by METTL3, METTL16, and METTL5 together with the contribution of additional subunits of the mA system, has shown a dramatic impact on cancer development. However, the cellular localization of mA proteins inside tumor cells has been little studied so far.

Correction: Zwergel et al. Novel Quinoline Compounds Active in Cancer Cells through Coupled DNA Methyltransferase Inhibition and Degradation. 2020, , 447.

In the original publication [...

Targeting ROS production through inhibition of NADPH oxidases.

NADPH oxidases (NOXs) are transmembrane enzymes that are devoted to the production of reactive oxygen species (ROS). In cancers, dysregulation of NOX enzymes affects ROS production, leading to redox unbalance and tumor progression. Consequently, NOXs are a drug target for cancer therapeutics, although current therapies have off-target effects: there is a need for isoenzyme-selective inhibitors.

SIRT1 activation promotes energy homeostasis and reprograms liver cancer metabolism.

Background: Cancer cells are characterized by uncontrolled cell proliferation and impaired bioenergetics. Sirtuins are a family of highly conserved enzymes that play a fundamental role in energy metabolism regulation. SIRT1, in particular, drives many physiological stress responses and metabolic pathways following nutrient deprivation.

2-Substituted 1,5-benzothiazepine-based HDAC inhibitors exert anticancer activities on human solid and acute myeloid leukemia cell lines.

Herein, we report the development of a new series of histone deacetylase inhibitors (HDACi) containing a 2-substituted 1,5-benzothiazepine scaffold. First, a virtual combinatorial library (∼1.6 × 10 items) was built according to a convenient synthetic route, and then it was submitted to molecular docking experiments on seven HDACs isoforms belonging to classes I and II.

Sirtuin Inhibitor Cambinol Induces Cell Differentiation and Differently Interferes with SIRT1 and 2 at the Substrate Binding Site.

Epigenetic mechanisms finely regulate gene expression and represent potential therapeutic targets. Cambinol is a synthetic heterocyclic compound that inhibits class III histone deacetylases known as sirtuins (SIRTs). The acetylating action that results could be crucial in modulating cellular functions via epigenetic regulations.

Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer.

A large body of clinical and experimental evidence indicates that colorectal cancer is one of the most common multifactorial diseases. Although some useful prognostic biomarkers for clinical therapy have already been identified, it is still difficult to characterize a therapeutic signature that is able to define the most appropriate treatment. Gene expression levels of the epigenetic regulator histone deacetylase 2 () are deregulated in colorectal cancer, and this deregulation is tightly associated with immune dysfunction.

Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets.

In recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of cancer. However, the administration of drugs in cancer patients requires careful evaluation since their interaction with individual biological macromolecules, such as proteins or nucleic acids, determines variable downstream effects.

Novel pyridine-containing histone deacetylase inhibitors strongly arrest proliferation, induce apoptosis and modulate miRNAs in cancer cells.

After over 30 years of research, the development of HDAC inhibitors led to five FDA/Chinese FDA-approved drugs and many others under clinical or preclinical investigation to treat cancer and non-cancer diseases. Herein, based on our recent development of pyridine-based isomers as HDAC inhibitors, we report a series of novel 5-acylamino-2-pyridylacrylic- and -picolinic hydroxamates and 2'-aminoanilides 5-8 as anticancer agents. The hydroxamate 5d proved to be quite HDAC3/6-selective exhibiting IC values of 80 and 11 nM, respectively, whereas the congener 5e behaved as inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) at nanomolar level.