# Palladium-catalysed synthesis of small-molecule epigenetic inhibitors as anticancer therapeutics

## TL;DR

This paper reviews recent advances in using palladium-catalyzed reactions to design and synthesize small-molecule drugs targeting epigenetic processes for cancer treatment.

## Contribution

The paper provides a comprehensive overview of palladium-catalyzed methods for creating epigenetic inhibitors, emphasizing practical strategies for drug design.

## Key findings

- Palladium-catalyzed reactions are versatile for constructing drug-like molecules targeting epigenetic pathways.
- Optimization of ligand structure, base, and solvent significantly impacts the efficiency of these reactions.
- The review highlights strategies for developing selective and hybrid epigenetic inhibitors and degraders.

## Abstract

Palladium-catalysed reactions have emerged as indispensable tools in medicinal chemistry, enabling the precise construction of C-C and C-N bonds across a wide spectrum of drug-like molecular frameworks. This manuscript comprehensively examines advances reported over the past five years in palladium-catalysed methodologies applied to epigenetic drug discovery. The mechanistic diversity and synthetic adaptability of palladium catalysts for accessing scaffolds addressing the epigenetic targets have been highlighted. The robust drug design strategies and activity profile of the generated small molecule epigenetic inhibitors through palladium-assisted synthetic protocol are also presented in this compilation. Particular emphasis is placed on understanding the influence of ligand structure, base selection, and solvent optimisation in modulating catalyst reactivity. Collectively, this review offers a practical and forward-looking framework for the design and synthesis of next-generation epigenetic anticancer therapeutics (selective/non-selective/hybrid-inhibitors and degraders/PROTACS).