Allosteric Modulation of the Human Cannabinoid-1 Receptor by ORG27569

Allosteric Modulation of the Human Cannabinoid-1 Receptor: Negative Modulators, Positive Modulators, and Everything in Between!

On October 31st, I attended a lecture given by a PhD student, Derek Shore, here at UNCG. He talked about his research regarding the Human Cannabinoid-1 Receptor and a specific allosteric modulator: ORG27569. An allosteric modulator indirectly affects a receptor by binding to a separate area on the receptor and changing the conformation of the binding site. A positive modulator increases binding and acts as an agonist. A negative modulator decreases binding or decreases the effects of the molecule that is bound to the primary binding site. It acts as an antagonist. ORG27569 binds allosterically to the Cannabinoid-1 Receptor and then causes the active site of the receptor to change into an intermediate conformation. ORG27569 then also sterically hinders other processes that would result in receptor activation. All of these receptor sites are protein receptors that extend through the phospholipid bilayer of cells. This finding is very important in the world of pharmacology because this type of allosteric binding can be used to prevent side effects from occurring with many different kinds of drugs. This way, a drug can more effectively target what it needs to target without changing the balance of something else elsewhere. The lecture was very interesting, but I feel like I need a lot more chemistry to fully understand the mechanics of exactly what was going on. Although the uses of this research will not be used to test drugs on humans for many years, it will be interesting to see how this research will change the new generation of pharmaceuticals. 

Picture Source:
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