2-Pyridones wereselected for a screening program to identify nonpeptidicsmall molecules able to potently activate GHS-R1a in vitro in both transfected human cells and mouse hypothalamic cells andto induce in vivo orexigenic effects.56 In particular, the lead compound 18 (Figure 9A) showeda significantly increased food intake following intraperitoneal administrationin male C57BL/6J mice and may represent a potential tool for the treatmentof cachexia. This evidence concerns the gene GHSR and Cachexia.