Targeting autophagy drug discovery: Targets, indications and development trends

Area of Science:

• Cellular Biology
• Pharmacology
• Drug Development

Background:

• Autophagy is essential for cellular homeostasis; its dysregulation is linked to numerous diseases.
• Despite decades of research and drug development, no specific autophagy-modulating interventions are clinically available.
• Challenges in drug development stem from the complex effects of autophagy regulators in disease contexts.

Purpose of the Study:

• To review and analyze autophagy-targeted drugs based on their targets within the autophagic signaling network.
• To highlight drugs in preclinical or clinical trials, including those for monotherapy and combination treatments.
• To critically examine emerging drug designs targeting selective autophagy receptors (SARs) for various diseases.

Main Methods:

• Review of literature on autophagy-targeted drugs.
• Analysis of drug targets at different levels of the autophagic pathway (upstream, downstream, enzyme activities).
• Focus on agents in preclinical and clinical development, including combination therapies.

Main Results:

• Several promising compound categories for autophagy-based therapy have emerged due to new technologies.
• Drugs targeting specific autophagy pathways and combinations with existing therapies are emphasized.
• Emerging strategies focus on selective autophagy receptors (SARs) for treating cancer, inflammation, neurodegeneration, and metabolic disorders.

Conclusions:

• Autophagy-targeted drug development faces challenges due to pathway complexity.
• New technologies and strategies, particularly targeting SARs, offer promise for treating diverse diseases.
• Future perspectives include optimizing drug design and exploring combination therapies for clinical application.