Indole therapeutics: Latest FDA updates, ongoing trials, and future directions

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Drug Discovery

Background:

• Indole scaffolds are crucial pharmacophores in various therapeutic areas, including oncology, virology, neurology, and metabolic disorders.
• The clinical landscape of indole-based drugs has seen significant evolution over the past decade, influenced by regulatory actions and emerging health challenges like the COVID-19 pandemic.

Purpose of the Study:

• To systematically review FDA-approved, withdrawn, and investigational indole-containing drugs from the last decade.
• To analyze evolving clinical outcomes, regulatory trends, and therapeutic repositioning of indole-based pharmaceuticals.
• To provide a framework for future development and optimization of indole scaffolds for multi-target therapies.

Main Methods:

• Systematic literature review of indole-containing drugs.
• Analysis of FDA approvals, withdrawals, and clinical trial data.
• Evaluation of pharmacological classes, structural characteristics, and therapeutic outcomes.

Main Results:

• A shift from cytotoxic to targeted anticancer indole agents has been observed.
• Indole-based antivirals have gained prominence, particularly in response to the COVID-19 pandemic.
• Growing interest in neuroactive indoles, including psychedelic compounds, alongside progress in epigenetic and metabolic modulators. Underrepresentation of indole-based antibiotics noted.

Conclusions:

• Indole scaffolds demonstrate remarkable versatility and adaptability in drug development.
• Future research should focus on optimizing indole structures for enhanced efficacy and exploring multi-target applications.
• Strategic development of indole-based drugs is essential to address unmet medical needs across diverse therapeutic areas.