PYY analogue - Y2 selective

PYY is secreted from the L-cells in the intestine in response to a meal. The PYY1-36 is rapidly cleaved to PYY3-36 and this analogue bind and activate selectively the Y2 receptor. PYY3-36 is also quite rapidly degraded to the inactive version PYY3-34. The Y2 receptor belongs to a the NPY family of receptors that comprise four receptors Y1, Y2 Y4 and Y5. It is a satiety factor and lowers food intake as well as glucose regulation. In combination with GLP-1 which is also co-secreted from the L-cells the effects are potentiated.

NNC0165-1273 is a modified PYY3-36 analogue with increased selectivity for Y2 against Y1, Y4 and Y5 receptors. It is modified in the C-terminal position 35 where the arginine has been replaced with beta-homo-arginine and Leu30 has been replaced by Trp30. In the Østergaard et al. 2018 reference listed in the reference section, NNC0165-1273 is peptide 29. The C-terminal modification results in a slightly lower Y2 activity, but much improved selectivity and it also stabilizes against C-terminal degradation.