Targeting Epigenetic Complexes and Alternative Protein Degradation Pathways in Medicinal Chemistry
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".
Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 938
Special Issue Editor
Special Issue Information
Dear Colleagues,
The development of novel therapeutic strategies that modulate intracellular protein homeostasis and epigenetic regulation is opening unprecedented avenues in medicinal chemistry. Beyond classical PROTACs and HDAC inhibitors, recent efforts have unveiled emerging platforms such as LYTACs, AUTACs, ATTECs, and small-molecule modulators of chromatin remodeling complexes (e.g., NuRD, SWI/SNF, PRC2). These non-canonical degradation mechanisms and epigenetic regulators play critical roles in the progression of cancer, infectious diseases, and neurological disorders.
This Special Issue aims to highlight advances in the discovery and development of small molecules, hybrid compounds, conjugates, or molecular tools targeting either non-proteasomal degradation pathways or epigenetic protein complexes. Submissions may focus on molecular design, synthesis, SAR studies, mechanistic investigations, or therapeutic evaluation.
This Special Issue invites contributions that explore innovative small molecules, conjugates, and biologically active compounds designed to target these underexplored systems. We welcome original research and review articles covering:
- Inhibitors and degraders targeting chromatin remodeling complexes (e.g., CHD4, HDACs, EZH2, BRD proteins);
- Non-proteasomal degradation strategies: lysosome-targeting chimeras (LYTACs), autophagy-tethering compounds (AUTACs/ATTECs);
- Molecular mechanisms linking epigenetic control and protein stability;
- Rational design, synthesis, SAR studies, and degradation kinetics;
- Therapeutic applications in cancer, neurodegeneration, infectious and neglected diseases;
- Delivery systems or conjugates enabling selective engagement of epigenetic or degradation targets.
Dr. Jean Leandro Dos Santos
Guest Editor
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Keywords
- protein degradation
- LYTAC
- AUTAC
- ATTEC
- epigenetics
- NuRD
- HDAC
- BRD
- SWI/SNF
- PRC2
- chromatin
- conjugates
- lysosome
- autophagy
- drug discovery
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