Targeting oncogenic protein-protein interactions by diversity oriented synthesis and combinatorial chemistry...

Area of Science:

• Oncology
• Medicinal Chemistry
• Molecular Biology

Background:

• Anticancer drug development is declining due to cancer's complexity and heterogeneity.
• Protein-protein interactions (PPIs) are crucial in cellular processes and implicated in cancer.
• Targeting multiple PPIs offers a promising strategy beyond single-target approaches.

Purpose of the Study:

• To review chemistry-driven strategies for discovering small molecules that disrupt oncogenic PPIs.
• To highlight the role of diversity-oriented synthesis (DOS) in modulating biological hubs.
• To focus on key cancer-related PPIs such as p53-Mdm2 and Bcl-2/Bcl-xL-BH3.

Main Methods:

• Exploration of diversity-oriented synthesis (DOS) and combinatorial chemistry approaches.
• Focus on small molecule design targeting specific oncogenic protein-protein interactions.
• Review of literature on chemistry-driven methods for PPI disruption.

Main Results:

• Identification of key oncogenic PPIs as therapeutic targets.
• Demonstration of chemistry-driven approaches to access diverse chemical space.
• Potential for multi-functional scaffolds to modulate multiple PPIs.

Conclusions:

• Novel anticancer drug discovery requires innovative strategies beyond single-target drugs.
• DOS and combinatorial approaches are vital for developing modulators of oncogenic PPIs.
• Targeting PPIs offers a promising avenue for future cancer therapeutics.