Our lab's mission is to discover and validate transformative therapeutic targets, with the ultimate goal of creating safe and effective new drugs for pain, inflammation, neurodegeneration and psychiatric disorders.
Recent examples of our work include:
- N-acylethanolamine acid amidase (NAAA). NAAA is a cysteine amidase that catalyzes the degradation of two endogenous analgesic and anti-inflammatory lipids, palmitoylethanolamide and oleoylethanolamide. NAAA is mainly expressed in cells of the immune system. Our group has discovered the first classes of potent and selective NAAA inhibitors and demonstrated that these agents cause profound analgesic and anti-inflammatory effects in animal models. These compounds were out-licensed to a biopharmaceutical company in the US, and one of them is undergoing preclinical development. We continue to investigate the roles of NAAA and explore its value as a therapeutic target.
- Peripherally restricted fatty acid amide hydrolase (FAAH) inhibitors. FAAH is a serine amidase that degrades the endogenous cannabinoid anandamide. We discovered the first systemically active inhibitor for this enzyme in 2003 and, more recently, we identified a new group of FAAH inhibitors that do not enter the brain and spinal cord. These peripherally restricted agents produce marked analgesia in animal models, without any of the side effects of current painkillers. The lead compound in this class is scheduled to start preclinical development in 2016.
- Acid ceramidase (AC). AC is a cysteine amidase that degrades the sphingolipid messenger ceramide, into sphingosine and fatty acid. Ceramide plays a key role in the control of cellular senescence and programmed cell death. For this reason, AC inhibitors offer hope in the treatment of disease states characterized by dysregulated cell proliferation. We created the first classes of potent and selective AC inhibitors, including systemically active compounds that were recently out-licensed to a biopharmaceutical company in the US.
- Multi-target FAAH and cyclooxygenase (Cox) inhibitors. We have shown that simultaneous inhibition of FAAH and Cox activities with designed multi-target agents, provides an effective and safe strategy to treat inflammatory bowel disease, a non-resolving inflammatory conditions that is currently undertreated.