Repurposing FDA-approved drugs to inhibit PRL-3, Scientific Reports (2021)

A major goal of our lab’s PRL-3 projects is to find a way to inhibit PRL-3 activity. PRL-3 is essential for the growth and spread of many types of cancer, so if we can find a way to block PRL-3, we could potentially impact many patients. However, the drugs used to target PRL-3 are still under development and years away from the clinic. To speed the process of bringing a new PRL-3 inhibitor to cancer patients, we screened a panel of 1,400 FDA-approved drugs to find those that could be repurposed to block PRL-3 activity. Our two best hits inhibited PRL-3 phosphatase activity and prevented cancer cells from migrating. These drugs inhibited the PRL family but did not target other phosphatases. Unfortunately, with our two best hits, the amount of drug needed to block PRL-3 activity were in the micro-molar range, which would be too much to give to patients. On an exciting note, though, we did find that one of our inhibitors, Candesartan, bound PRL-3 at a previously undiscovered allosteric site! An allosteric inhibitor does not bind in the PRL-3 active site but still blocks PRL-3 function. This information is very useful to our chemistry collaborators as they work to design new PRL-3 inhibitors. So, even if this project didn’t work out exactly as we had hoped, we still found something new and are getting a little closer to our goal of targeting PRL-3 in cancer.

Click here to check out our manuscript!