Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3.

ABSTRACT: The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r-/- mice. F

SUBMITTER: Montero-Melendez T 

PROVIDER: S-EPMC5346439 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature