rockville: About 80,000 Americans die of overdoses each year, and nearly three million Americans battle opioid use disorder. Opioid medications that bind to opioid receptors include heroin, fentanyl, oxycodone, and morphine.
Activation of the mu opioid receptor causes euphoria and pain relief, as well as physical dependence and sluggish breathing, the latter of which can lead to death from drug overdose. Blockade of kappa opioid receptors may be a promising pharmaceutical strategy to treat opioid dependence, based on preclinical studies.
By discovering drugs that inhibit the kappa opioid receptor, Leslie Salas Estradain the laboratory of Marta Filizolaat the Icahn School of Medicine at Mount Sinai, hopes to alleviate opioid addiction. roadside roomsa postdoctoral researcher, will present her work on Monday, February 20, at the 67th Annual Meeting of the Biophysical Society in San Diego, California.
Kappa opioid receptors are known to mediate brain rewards. “If you’re addicted and you’re trying to quit, at some point you’ll have withdrawal symptoms, and they can be very difficult to overcome,” Salas Estrada explained, “after a lot of exposure to opioids, your brain rewires itself to need more drugs. Blocking kappa opioid receptor activity in animal models has been shown to reduce this urge to use drugs in the withdrawal period.”
However, discovering drugs that can block the activity of a protein, such as the kappa opioid receptor, can be a long and expensive process. Using computer tools can make it more efficient, but it can take months to detect billions of chemical compounds. Instead, Salas Estrada is using artificial intelligence (AI) to streamline the process. \
“Artificial intelligence has the advantage of being able to take large amounts of information and learn to recognize patterns from it. Therefore, we believe that machine learning can help us harness information that can be derived from large chemical databases to design new drugs from it. zero. And in that way, we can potentially reduce the time and costs associated with drug discovery,” she said.
Using information about the kappa opioid receptor and known drugs, they trained a computer model to generate compounds that could block the receptor with a reinforcement learning algorithm that rewarded properties that are favorable for drug treatments.
So far, the team has identified several compounds that have promising properties, and they are working with collaborators to synthesize them and eventually test their ability to block the kappa opioid receptor in cells, before testing them in animal models for safety and efficacy. Ultimately, Salas Estrada said, “we hope that we can help people who are struggling with addiction.”
