Bye-Bye Diseased Proteins: PROTACs Explained

PROTACs are one of the most exciting new drug technologies in biotech. Instead of blocking disease-causing proteins, they eliminate them entirely. That shift—from inhibition to destruction—could unlock treatments for diseases previously considered “undruggable.” Let’s break it down.

What It Is

PROTAC stands for Proteolysis Targeting Chimera. In simple terms, a PROTAC is a two-headed molecule connected by a linker:

• One end binds to a disease-causing protein
• The other end binds to a protein disposal system inside the cell

The molecule acts like a molecular matchmaker, bringing the bad protein to the cell’s garbage disposal system. That disposal system is called the ubiquitin-proteasome system, the cell’s built-in recycling machinery. Once tagged, the protein is destroyed.

Why It Matters

Traditional drugs usually block proteins. PROTACs remove them entirely. Think of it this way:

How It Works

Disease often occurs because a protein is doing something harmful, such as driving cancer cell growth, causing inflammation, and damaging neurons. PROTACs solve the problem by removing the protein itself.

The steps:

1. Binding: On one end the PROTAC binds the disease protein.
2. Recruitment: The other end of the PROTAC recruits an E3 ubiquitin ligase, a protein tagging enzyme.
3. Tagging: The E3 ubiquitin ligase attaches ubiquitin molecules to the target protein.
4. Destruction: The cell’s proteasome recognizes the ubiquitin tag and destroys the protein.

Afterward, the PROTAC molecule is released and can repeat the process. One PROTAC molecule can eliminate many proteins. That efficiency is why scientists are so excited about this approach.

In Development

PROTAC therapies are currently being developed for several major disease categories.

Cancer: The most advanced clinical programs target cancer proteins that drive tumor growth. Some early PROTAC drugs are already in clinical trials for prostate and breast cancer. Examples include:

• Androgen receptor (AR) – prostate cancer
• Estrogen receptor (ER) – breast cancer
• BRD proteins – multiple cancers
• BTK – blood cancers

Neurodegenerative Diseases: PROTACs may help eliminate toxic proteins linked to diseases like Alzheimer’s, Parkinson’s and Huntington’s disease. These conditions are driven by proteins that accumulate in the brain, making them ideal targets for degradation technologies.

Inflammatory and Autoimmune Diseases: Researchers are also exploring PROTACs for rheumatoid arthritis, lupus, and chronic inflammatory diseases by degrading signaling proteins that drive inflammation.

The Pioneers

Several biotech companies have built entire platforms around targeted protein degradation, including:

• Arvinas was the first company to bring PROTAC drugs into human clinical trials. Lead programs include degraders targeting androgen receptors for prostate cancer and estrogen receptors for breast cancer.
• Nurix Therapeutics focuses on controlling the ubiquitin-proteasome system. Their programs target blood cancers and immunological diseases.
• Kymera Therapeutics develops degraders for immunology and oncology. Focus areas include IRAK4 degraders for autoimmune diseases and STAT protein degraders for cancer.

Become Biotech Fluent

Technologies like PROTACs are built on core concepts in drug discovery, molecular biology, and protein regulation. Once you understand these fundamentals, you can understand:

• How new therapies are discovered
• Why certain drugs succeed or fail
• Where the biggest biotech opportunities are emerging

Become fluent in the science driving modern biotech. Explore Biotech Primer’s training programs for your team and gain the knowledge to confidently engage in the business of life science innovation.