Table 4.

Pharmacological evaluation of SRB103H3 vs SRB103. Mean ± SEM parameter estimates from 3-parameter fitting of data from Figure 3, Figure 4 and association rate constants for kinetic data where relevant. Statistical comparisons performed by paired t-tests comparing SRB103Q vs SRB103H. If both ligands were full agonists, Emax values are shown after re-fitting data normalised to the globally fitted maximum response. If only one ligand was a full agonist, statistical comparison was performed prior to normalisation, but the numerical results are presented after normalisation to the full agonist response. ∗p < 0.05 indicated by the statistical test.

	SRB103H			SRB103Q
	pEC50 (M)	Emax	K@[max] (min-1)	pEC50 (M)	Emax	K@[max] (min-1)
GLP-1R mini-Gs (HEK293T)	7.1 ± 0.1	103 ± 4	0.93 ± 0.29	7.3 ± 0.1	97 ± 3	0.70 ± 0.20∗
GLP-1R βarr2 (HEK293T)	6.4 ± 0.1	100	0.37 ± 0.06	6.7 ± 0.0∗	60 ± 2∗	0.39 ± 0.05
GCGR mini-Gs (HEK293T)	8.1 ± 0.1	100	0.14 ± 0.01	7.7 ± 0.1∗	83 ± 1∗	0.13 ± 0.01
GCGR βarr2 (HEK293T)	7.5 ± 0.1	100	0.81 ± 0.07	7.3 ± 0.1∗	77 ± 2∗	0.71 ± 0.06∗
GLP-1R cAMP (CHO–K1)	9.5 ± 0.1	99 ± 4	n.c.	9.5 ± 0.1	103 ± 2	n.c.
GCGR CAMP (CHO–K1)	9.6 ± 0.2	107 ± 5	n.c.	9.4 ± 0.2	103 ± 4	n.c.
GIPR CAMP (CHO–K1)	7.6 ± 0.2	101 ± 5	n.c.	7.0 ± 0.1∗	92 ± 9	n.c.
DERET (HEK293-SNAP-GLP-1R)	7.7 ± 0.2	3.0 ± 0.1	0.14 ± 0.02	7.7 ± 0.2	2.7 ± 0.2∗	0.5 ± 0.01∗
HCA assay (HEK293-SNAP-GLP-1R)	8.1 ± 0.1	86 ± 2		8.6 ± 0.0∗	79 ± 3∗
INS-1 832/3 cAMP, 10 min	8.1 ± 0.1	67 ± 6		8.2 ± 0.2	70 ± 7
Primary islet cells cAMP, 5 min	9.0 ± 0.4	1.7 ± 0.1		9.0 ± 0.4	1.6 ± 0.1
INS-1 832/3 insulin secretion, 16 h	8.8 ± 0.2	3.5 ± 0.3		9.3 ± 0.1∗	3.4 ± 0.4
Huh7-GCGR cAMP, 10 min	10.5 ± 0.2	27 ± 4		10.8 ± 0.2∗	27 ± 4
Huh7-GCGR cAMP,16 h	9.6 ± 0.2	173 ± 11		9.7 ± 0.2	284 ± 38∗
cAMP 10 min (primary hepatocytes)	9.4 ± 0.1	170 ± 7		8.9 ± 0.1∗	175 ± 12
cAMP 16 h (primary hepatocytes)	7.6 ± 0.1	206 ± 7		7.5 ± 0.0	200 ± 6