Hitting the Mark—Targeting a Protein for Relief?

The FK506-binding protein 51, or FKBP51 has been implicated as a causal agent for chronic pain, obesity, and major depression, but until now it has not been possible to inhibit this protein without affecting other similar proteins. But new research using mouse models has identified a specific inhibitor, SAFit2, that appears to target only the FKBP51 protein. Principal Investigator Felix Hausch, PhD, with the Technical University of Darmstadt, commented, “The FKBP51 protein plays an important role in depression, obesity, diabetes, and chronic pain states. We developed the first highly potent, highly selective FKBP51 inhibitor, called SAFit2, which is now being tested in mice. Inhibition of FKBP51 could thus be a new therapeutic option to treat all of these conditions.” Findings from the work were scheduled for presentation yesterday at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition.

FKBP51 is expressed at various points in the body, including the brain, skeletal muscle tissue, and fat. It can inhibit glucose uptake and fat burning, as well as impacting stress responses. A close relation, FKPB52 exerts the opposite effect on cells, and thus selectivity in targeting the former without affecting the latter was viewed by the researchers as a crucial objective. Using nuclear magnetic resonance techniques, the team detected a previously unknown binding site in FKBP51 for which they developed SAFit2 as an inhibitor. In 3 mouse model tests, introduction of SAFit2 was found to protect against weight gain, facilitate better stress coping behaviors, and reduce pain sensation.

Read about the research findings.