Kate Bowman
Discovering Prokineticin Receptor 2 Agonists for the Treatment of Obesity
Abstract
Rates of obesity are rising worldwide, however effective weight-loss medications are limited. Therefore, it is urgent to find new therapeutic targets to promote safe and sustained weight loss. Prokineticin 2 (PK2) is an endogenous anorexigenic neuropeptide that activates two G-protein coupled receptors, prokineticin receptors (PKR) 1 and 2. We have shown that the anorexigenic effect of PK2 is mediated through activation of PKR2 in amygdala neurons, establishing PKR2 as a promising new target for the development of anti-obesity drugs. Inhibition of food intake by PKR2 is independent from the canonical melanocortin system, thus representing a yet unexplored avenue to screen small molecules with the goal of identifying PKR2 agonists. After validation of identified hits, chemical optimization will be performed to advance lead molecules towards drug development. Completion of this project will yield novel anorexigenic compounds acting through a newly identified pathway controlling feeding.
I am immensely grateful to the PhRMA Foundation for supporting not only my research but also my scientific career. The predoctoral fellowship will propel me further into the world of drug discovery and the innovation of novel translational treatments.
