Novel anticancer targets and drug discovery in post genomic age

Area of Science:

• Oncology
• Medicinal Chemistry
• Drug Discovery

Background:

• Cancer remains a significant global health threat with complex origins.
• Advances in chemogenomics and human genome sequencing are driving the discovery of novel anticancer targets.
• New Drug Discovery (NDD) is transitioning from a gene-centric to a drug-centric approach.

Purpose of the Study:

• To review the progress in identifying anticancer targets and discovering new drugs.
• To highlight the role of biological macromolecular targets in cancer therapy.
• To present novel peptidomimetic inhibitors targeting Matrix Metalloproteinases (MMPs) and Aminopeptidase N (APN).

Main Methods:

• Review of current chemogenomic strategies for anticancer drug discovery.
• Focus on key targets including MMPs, Aminopeptidase N (APN), Tyrosine Kinase (TK), and Farnesyltransferase (FTase).
• Design and synthesis of peptidomimetic inhibitors (MMPIs and APNIs) with specific molecular scaffolds (pyrrolidine, AHPA, glutamylide).

Main Results:

• The study extensively investigated MMP-2, MMP-9, and APN as therapeutic targets.
• Novel pyrrolidine-based Matrix Metalloproteinase Inhibitors (MMPIs) were designed and synthesized.
• The pyrrolidine scaffold demonstrated potent inhibition against MMP-2 and MMP-9, with IC(50) values ranging from 1 nM to 300 nM.

Conclusions:

• The development of targeted anticancer therapies is advancing rapidly.
• Peptidomimetic inhibitors, particularly those with a pyrrolidine scaffold, represent a promising class of anticancer agents.
• These novel inhibitors offer potential for effective treatment strategies against cancer growth and metastasis.