World’s first FDA-approved therapy based on PROTAC technology

The U.S. Food and Drug Administration (FDA) has approved vepdegestrant for the treatment of patients with ESR1-mutated, estrogen receptor (ER)-positive, and HER2-negative advanced breast cancer.

• Vepdegestrant is the world’s first FDA-approved therapy based on PROTAC (Proteolysis Targeting Chimera) technology, marking a major breakthrough in targeted drug development.
• Unlike conventional medicines that merely block the activity of disease-causing proteins, PROTAC-based drugs eliminate the harmful proteins from cells, offering a new therapeutic approach.
• The approval is considered a significant advancement because PROTAC technology can target previously “undruggable” proteins, expanding treatment options for several diseases.
• Researchers have been developing PROTAC technology for more than two decades.

About PROTAC Technology

• PROTAC (Proteolysis Targeting Chimera) is a class of heterobifunctional molecules designed to selectively degrade disease-causing proteins by harnessing the cell’s ubiquitin-proteasome system (UPS).
• A PROTAC molecule consists of two functional ends (heads) connected by a chemical linker.
• One end binds specifically to the target protein, while the other recruits an E3 ubiquitin ligase, an enzyme involved in protein degradation.
• The PROTAC molecule brings the target protein and the E3 ubiquitin ligase into close proximity, allowing the target protein to be tagged with ubiquitin.
• The ubiquitin tag directs the protein to the proteasome, the cell’s natural protein recycling and waste disposal machinery, where it is broken down and removed.
• By degrading rather than merely inhibiting disease-causing proteins, PROTAC technology offers the potential for more durable therapeutic effects, lower drug resistance, and treatment of diseases involving proteins that were previously difficult to target.

Sources: The Hindu & Astrazeneca

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