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Novel Compound Could Produce New Autoimmune Therapies

By Ryan Bushey | November 22, 2017

Researchers have uncovered a unique compound that may yield a class of revolutionary treatments targeting autoimmune conditions.

Scientists from the University of Colorado Boulder performed a screening where they sifted through 14,000 small molecule compounds to find a chemical structure that could bind to a protein called the Toll-like receptor 8 (TLR8), which is believed to play an important in the innate immune response for bodies to start attacking its own tissue.

Four molecules surfaced with similar structures, but further chemically synthesizing a number of novel compounds revealed the final choice that was a molecule called CU-CPT8m.

A study was performed where the researchers found the molecule could bind to and inhibit TLR8 along with exerting “potent anti-inflammatory effects” on the tissue of patients who have arthritis, osteoarthritis, and Still’s disease.

“Our study provides the first small molecule tool to shut this protein down so we can understand its pathogenesis,” said lead author Hang Hubert Yin, a biochemistry professor in the BioFrontiers Institute, in a statement.

TLR8 has a unique molecule structure. It’s hidden inside the infinitesimal bubble instead of on the cell’s surface making it an extremely difficult target for drug development.

Other efforts to attack this protein have primarily focused on shutting it down when it is in its active state. TLR8 will go through a transformation from its passive to active state when it senses the presence of a bacteria or virus. This triggers a deluge of inflammatory signals to fend off what it deems a foreign invader, but that ends up leading to the onset of disease when that response is excessive.

By contrast, the compound Yin and his team found prevents it from activating while still in its passive state.

Yin noted this discovery could be “paradigm shifting” since the three of the top five selling drugs in the U.S. are designed to ease these symptoms. Plus, these treatments can be expensive and come saddled with side effects.

“Before, people were trying to close the open door to shut it down. We found the key to lock the door from the inside so it never opens,” said Yin.

A patent application has been filed with the hope of moving on to animal studies and clinical trials within the next two years.

The study was published in the journal Nature Chemical Biology.


Filed Under: Drug Discovery

 

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