Scientists at Heptares Therapeutics have figured out the molecular structure of the CCR9 receptor, an immune cell inflammatory protein associated with several diseases, including IBD. Knowing the structure of this protein may lead to the development of novel therapies for these diseases.
CCR9 is a chemokine receptor that belongs to a family of proteins called the G protein-coupled receptors (GPCRs). These proteins participate in immune defense by managing the migration, activation, and survival of immune cells and are considered valuable targets for therapies aimed at reducing inflammation.
The CCR9 receptor, for example, plays a role in recruiting immune cells to the gut, a process that contributes to inflammatory bowl disease (IBD).
Although the pharmaceutical industry has made significant efforts to develop novel drugs targeting chemokine receptors, only two compounds have reached the market: Selzentry (maraviroc) for HIV infection and Mozobil (plerixafor) for stem-cell transplant mobilization.
This low achievement may be due to the lack of knowledge about the structure of chemokine receptors, which limits the ability to improve compounds that target their activity.
The study leading to the identification of CCR9’s structure was published in the journal Nature, titled “Intracellular Allosteric Antagonism Of The CCR9 Receptor.”
Researchers at Heptares used vercirnon, a selective blocker of the CCR9 receptor, to analyze the protein’s structure. The team found that vercirnon binds to the part of the protein located within the cell, preventing the receptor from interacting with other molecules inside the cell and propagating the signal for inflammatory processes.
Heptares believes the discovery of this novel binding site in the CCR9 receptor sheds new light on chemokine receptors and can help improve the success rate of newly developed drugs in the battle against inflammation.
“The availability of a high-resolution structure of the CCR9 receptor in this conformation provides a unique opportunity to apply structure-based drug design to the discovery and optimization of selective small molecule allosteric modulator drugs not only targeting CCR9 but potentially also other members of the chemokine receptor family,” Fiona Marshall, chief scientific offer at Heptares, said in a news release.
“This new structural information adds to the wealth of information [Heptares] has generated … on GPCRs, and is enabling the company to apply its structure-based design platform to develop a sustainable pipeline of novel drug candidates in diverse disease areas,” she added.
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