Molecular Gates are small molecule drugs that selectively eliminate harmful extracellular proteins at their origin, inside cells, and prevent them from emerging to cause disease.
The Secretory Translocon: A Ubiquitous and Singular Exit
The human body produces over 4,000 distinct extracellular proteins. Like all proteins, extracellular proteins are translated in the cytoplasm and then must cross a membrane to move from inside the cell to the outside. They make this journey via a single channel in the endoplasmic reticulum, called the secretory translocon.
Extracellular Proteins Drive Many Diseases
Extracellular proteins are drivers of many human diseases, ranging from inflammatory conditions to neurodegenerative disease to several cancers. In fact, over 1,000 extracellular proteins are linked to a disease. Extracellular proteins can cause disease when they:
act improperly
fold incorrectly
are produced at levels that are too high
or are secreted at the wrong time or place in the body
If the proteins causing these problems could be eliminated, these diseases could be treated or even potentially cured.
Stopping Diseases at Their Origin
Molecular Gates eliminate disease-causing proteins by blocking them at their source: inside the cell. Our medicines do this by binding to the secretory translocon and setting up a “gate” in the channel.
The Molecular Gate recognizes the specific amino acid sequence of a disease-causing protein, and selectively disrupts its journey through the channel. With nowhere to go, the protein is degraded by the cell, ultimately eliminating the disease-causing protein.
The Small Molecule Advantage
Gate’s new mechanism opens therapeutic paths for diseases that can’t be treated today or where existing treatments are sub-optimal for patients.
To eliminate extracellular proteins today requires biologic therapies, like antibodies or RNA drugs, that can be difficult to deliver to the right place at the right time.
In contrast, because they are small molecules, Molecular Gates can access all tissues including the brain (if needed) and be taken orally as a convenient pill instead of injected.
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