Amount per vial
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It is modified in the C-terminal position 35 where the arginine has been replaced with beta-homo-arginine and Leu30 has been replaced by Trp30.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.
Amount per vial
(compared to reference)
|30 tryptophan and 35-beta-homo-arginine||-|
|Extinsion coefficient (calculated, 280nm)||11460||11460|
Figure 12D sketch of NNC0165-1273. Compared to native PYY, NNC0165-1273 has a beta-homo-arginine in position 35.
Figure 22D sketch of the sequence of native PYY (3-36)-NH2.
NPY receptor scintillation proximity assays (SPA) were performed using cell membrane preparations from cell lines expressing one of the human Y1, Y2, Y4, or Y5 receptors. Reduction of cyclic adenosine monophosphate (cAMP) through Gi-coupled Y receptor activation was measured using human embryonic kidney (HEK) 293 cells stably expressing one of the human Y1, Y2, Y4, or Y5 receptors and a cAMP-sensitive calcium channel. See the Østergaard et al. 2018 reference listed in the reference list for further data and details on the experimental setup of the in vitro assays.
||Receptor binding data (K i , nM)|
||Potency data (EC50, nM)|
For in vivo data, please see the Jones et al. 2019 reference listed in the reference section.