Table 1.

In vitro receptor activation of human-specific receptors by novel long-active triple agonists, compared to the native ligand for each receptor. X = 2-aminoisobutyric acid; B = K[OEG-OEG-γGlu-C18 diacid]; J = K[OEG-OEG-γGlu-C20 diacid]; Z = K[εLys-εLys-γGlu-C20 diacid].

Compound	Peptide Sequence	hGLP-1 Receptor		hGIP Receptor		hGcg Receptor
		EC50 (pM)	Relative Potency %	EC50 (pM)	Relative Potency %	EC50 (pM)	Relative Potency %
	Native ligand	6.9		10.4		9.5
4	YXEGT FTSDY SIYLD KQAAX EFVNW LLAGG PSSGA PPPSK(C16)—NH2	3.6	193	4.8	217	2333.8	0.4
5	YXQGT FTSDY SIYLD KQAAX EFVNW LLAGG PSSGA PPPSK(C16)—NH2	3.5	199	6.0	173	29.0	33
6	YXQGT FTSDY SIYLD KQAAX EFVNW LLAGG PSSGA PPPSB—NH2	11.7	59	44.5	23	703.4	1
7	YXQGT FTSDY SIYLD BQAAX EFVNW LLAGG PSSGA PPPS—NH2	7.4	93	27.4	38	81.9	12
8	YXQGT FTSDY SIYLD JQAAX EFVNW LLAGG PSSGA PPPS—NH2	6.8	101	26.7	39	163.4	6
9	YXQGT FTSDY SIYLEJQAAX EFVQW LLEGG PSSGA PPPS—NH2	3.1	220	11.4	92	185.0	5
10	YXQGT FTSDY SIYLEZQAAX EFVQW LLEGG PSSGA PPPS—NH2	2.8	244	7.0	150	86.6	11
11	YXHGT FTSDY SIYLEZQAAX EFVQW LLEGG PSSGA PPPS—NH2	106.4	7	7.1	147	72.1	13
12	HXQGT FTSDY SIYLEZQAAX EFVQW LLEGG PSSGA PPPS—NH2	1.7	410	55.0	19	357.1	3
13	HXHGT FTSDY SIYLEZQAAX EFVQW LLEGG PSSGA PPPS—NH2	2.0	340	7.1	146	48.7	19
14	HXHGT FTSDY SIYLEZKAAX EFVQW LLEGG PSSGA PPPS—NH2	3.3	211	7.3	142	13.7	69
15	HXHGT FTSDY SIYLEZQYAX EFVQW LLEGG PSSGA PPPS—NH2	6.8	101	7.7	135	13.1	72
16	HXHGT FTSDY SIYLEZKYAX EFVQW LLEGG PSSGA PPPS—NH2	3.9	177	15.6	67	9.3	102