Table 2. NPY Y₄R Agonist Potencies (EC₅₀) and Intrinsic Activities (α) or Antagonism (IC₅₀ Values).

	aequorin assaya		β-arrestin 1 assayb		β-arrestin 2 assayb
compd	EC50 or IC50 [nM]	α	EC50 or IC50 [nM]	α	EC50 or IC50 [nM]	α
hPP	9.7c	1	3.54 ± 0.59	1	2.74 ± 0.23	1
(2R,7R)-1	6.9c	0.62	40.4 ± 11	0.54	31.8 ± 12	0.58
2	49c	0.73	n.d.	n.d.	n.d.	n.d.
3	6390 ± 450	0.55	n.d.	n.d.	n.d.	n.d.
4	226d	n.a.	187 ± 72	n.a.	202 ± 78	n.a.
(2R,7R)-26e	388 ± 51	n.a.	5430 ± 350	n.a.	1320 ± 230	n.a.
27f	1430 ± 290	n.a.	1090 ± 350	n.a.	712 ± 87	n.a.
29	542 ± 110	0.07	875 ± 260	0.09	473 ±65	0.12
	572 ± 59	n.a.	n.d.	n.d.	n.d.	n.d.
31	1340 ± 530	n.a.	n.d.	n.d.	n.d.	n.d.
33	2050 ± 84	0.44	2200 ± 130	0.56	1790 ± 1070	0.61
34	1460 ± 83	0.61	1070 ± 520	0.62	568 ± 120	0.60
35	187 ± 23	0.58	144 ± 28	0.48	124.1 ± 24	0.55
36	303 ± 68	0.78	187 ± 40	0.51	140 ± 45	0.54
37	9580 ± 2000	n.a.	6640 ± 780	n.a.	8050 ± 120	n.a.
38	18 800 ± 6500	n.a.	1310 ± 390	n.a.	1120 ± 250	n.a.
39	8340 ± 2900	n.a.	n.d.	n.d.	n.d.	n.d.
40	6000 ± 2600	n.a.	n.d.	n.d.	n.d.	n.d.
41	608 ± 140	0.61	2050 ± 780	0.46	710 ± 200	0.49
42	756 ± 230	0.63	2160 ± 600	0.45	624 ± 150	0.56
44	12 400 ± 5500	n.a.	5390 ± 1630	n.a.	3940 ± 660	n.a.

^aAequorin calcium mobilization assay on CHO-hY₄-G_qi5-mtAEQ cells.²⁶ Antagonism (IC₅₀ values given in italics) was determined in the presence of 100 nM hPP (EC₅₀ = 9.7 nM).

^bβ-Arrestin 1,2 recruitment assay on HEK293T cells stably expressing the Y₄R and ARRB1 or ARRB2. Antagonism (IC₅₀ values given in italics) was determined in the presence of 3 nM hPP (EC₅₀ (ARRB1) = 3.54 nM; EC₅₀ (ARRB2) = 2.74 nM).

^cEC₅₀ value reported by Kuhn et al.¹¹

^dReported as K_b = 20 nM by Keller et al.⁵

^eY₄R agonism on HEK293-hY₄R-CRE Luc cells (luciferase reporter gene assay): EC₅₀ = 176 ± 50 nM, α = 0.81.

^fY₄R agonism on HEK293-hY₄R-CRE Luc cells (luciferase reporter gene assay): EC₅₀ = 220 ± 73 nM, α = 0.75. Presented are mean values ± SEM from at least three independent experiments (performed in triplicate). n.a.: not applicable; n.d.: not determined.