Daily News Analysis ‘PROTAC Technology Opens a New Era in Drug Development’ : 7 July

Why in News:

• The United States Food and Drug Administration (USFDA) has approved vepdegestrant, the world’s first PROTAC-based drug for advanced breast cancer.

PROTAC Technology: Key Facts

• PROTAC: Proteolysis-Targeting Chimera; a technology that destroys disease-causing proteins instead of merely blocking them.
• How it Works:
  • One end binds to the target protein.
  • The other binds to an E3 ligase (enzyme involved in protein degradation).
  • The target protein is marked for destruction by the cell’s natural protein disposal system.
• Mechanism: Called Targeted Protein Degradation (TPD).
• Catalytic Action: A single PROTAC molecule can destroy multiple copies of the same protein, making it effective at lower doses.
• First Approved Drug: Vepdegestrant for ESR1 (Estrogen Receptor 1)-mutated, ER-positive (Estrogen Receptor-positive) and HER2-negative (Human Epidermal Growth Factor Receptor 2-negative) advanced breast cancer.
• Advantage: Can target many previously “undruggable” proteins that conventional medicines cannot effectively inhibit.
• Administration: Oral, once-daily tablet; more convenient than injectable hormone therapies.
• Applications: Being developed for cancer, neurodegenerative diseases, inflammatory disorders and muscle diseases.
• Challenges: Large molecular size, limited absorption, possible drug resistance and dependence on only a few E3 ligases despite humans having over 600 such enzymes.