Pharmacological Targeting of the Epigenetics-Metabolism Axis: Experimental Therapeutics and Drug Discovery

Energy metabolism reprogramming is a fundamental hallmark of various pathological conditions, including cancer, neurodegenerative diseases, metabolic disorders, and cardiovascular diseases. Recent advances have unveiled a bidirectional “epigenetic-metabolic” regulatory circuit, where epigenetic modifications govern the expression of metabolic enzymes, and metabolic intermediates in turn modulate epigenetic modifiers. To accelerate translation into clinical applications, this Research Topic focuses directly on the experimental pharmacology and drug discovery pipelines targeting this intricate axis.

While biological insights into this crosstalk are rapidly expanding, the translation of these findings into validated pharmacological targets and efficacious therapeutic agents remains the primary bottleneck. This Research Topic aims to bring together cutting-edge research establishing the preclinical and clinical pharmacology of agents targeting the epigenetics-metabolism interface. We seek studies that move beyond purely descriptive mechanism characterization to emphasize target validation, lead discovery, pharmacological intervention, and preclinical evaluation.

We welcome Original Research and Review articles focusing on (but not limited to):

Pharmacological validation and characterization of novel therapeutic targets within the epigenetic-metabolic circuit.

De novo drug discovery, high-throughput screening, and structure-based design of small molecules targeting epigenetic-metabolic regulators.

Drug repurposing (repositioning) strategies and synergistic drug combinations targeting epigenetic-metabolic homeostasis.

Experimental evaluation (in vitro and in vivo) of natural products, traditional medicines, and innovative biologics targeting this axis in disease models.

Translational pharmacology studies utilizing multi-omics to evaluate drug efficacy, safety, pharmacokinetics, and pharmacodynamics (PK/PD).

Development and preclinical validation of pharmacology-linked biomarkers for patient stratification and precision targeting of epigenetic-metabolic circuits.