. Author manuscript; available in PMC: 2024 Sep 20.

Published in final edited form as: J Am Chem Soc. 2023 Sep 11;145(37):20539–20550. doi: 10.1021/jacs.3c06703

Table 5.

GLP-1R Activation and NLuc-GLP-1R Affinity for GLP-1(7-36) and α/β/γ-Analogues 9 and 10.

	GLP-1R cAMP Production				NLuc-GLP-1R Affinity
Peptide	pEC₅₀	EC₅₀ (nM)	EC₅₀ relative	% Max	pIC₅₀	IC₅₀ (nM)	IC₅₀ relative
GLP-1(7-36)	10.0 ± 0.1	0.096	1	96 ± 4	7.3 ± 0.04	54	1
9	7.8 ± 0.1	16	167	69^[#]	6.5 ± 0.04	350	6
10	7.2 ± 0.3	62	646	61^[#]	6.2 ± 0.03	680	13

For GLP-1R activation, pEC₅₀, EC₅₀ and maximal response (% Max) represent the mean of ≥3 independent experiments. For NLuc-GLP-1R competition binding experiments, pIC₅₀ and IC₅₀ values are derived from ≥3 independent experiments. pEC₅₀ and pIC₅₀ indicate the negative logarithm of the half-maximal effective or inhibitory concentration (EC₅₀, or IC₅₀, respectively). EC₅₀ or IC₅₀ relative indicates cAMP potency or NLuc-GLP-1R affinity normalized to GLP-1(7-36) by the quotient (α/β/γ-analogue/GLP-1(7-36)). pEC₅₀, pIC₅₀ and % Max uncertainties are expressed as SEM. Symbol ^[#] describes the maximal response measured at the highest concentration (100 nM) for 9 or 10 when their corresponding dose-response curves failed to reach saturation.