Neuropeptide Y1 receptor (NPY1R) is one out of four receptors (NPY1R, NPY2R, NPY4R and NPY5R) that bind neuropeptide Y (NPY), an abundant neuropeptide in the mammalian central and peripheral nervous systems.

NPY1R is part of the β-branch of class A G-protein coupled receptors and likewise, has seven transmembrane domains with an extracellular N-terminus and intracellular C-terminal tail^1,2.

NPY belongs to a family of gut-brain peptides that demonstrate both hormonal functions by paracrine and endocrine release in the gastrointestinal tract and a neurotransmitter functions in sympathetic ganglia and the CNS. It is highly expressed throughout the brain with particularly high expression in limbic brain areas, such as the hippocampus, amygdala, and hypothalamus^3,4. NPY modulates multiple physiological and pathophysiological processes: it increases food intake and reduces fear and anxiety by activating NPY1R^1,2.

Because of the multiple functions of NPY, NPY1R has great importance in the development and progression of both metabolic and neurological diseases such as diabetes, obesity, breast cancer and bone loss and indeed a number of peptides and small-molecule compounds have been characterized as NPY1R antagonists and have shown clinical potential in the treatment of these pathological states⁵.