SUPPLEMENTARY INFORMATION In format provided by Conn et al. (SEPTEMBER 2014)

Table S2: Reported allosteric modulators of family B G-protein-coupled receptors

Receptor Modulator Example(s) GPCR Family B CRF1 receptor NBI 359651 NBI 27914;2 antalarmin;3 DMP696;4 SSR125543A;5,6 DMP904;7 NBI 30775/R1219198,9 CGRP receptor Compounds 1, 3 and 410 NOT Bay27-9955;11 L-168049 possibly DAB and CP-9114912 GLP1 receptor T-0632;49 NovoNordisk compound 1-6;13 compound 214; VU005655615

CGRP, gene related ; CRF1, corticotrophin releasing factor 1; GABA, γ-aminobutyric acid; GH, ; GLP-1, glucagon-like peptide 1; mAChR, muscarininc acetylcholine receptor, mGluR, metabotropic glutamate receptor

1 Hoare, S.R. et al. Allosteric ligands for the corticotropin releasing factor type 1 receptor modulate conformational states involved in receptor activation. Mol Pharmacol. 73, 1371-1380 (2008). 2 Hoare, S.R. et al. Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin- releasing factor1 (CRF1) receptor. Biochem Pharmacol. 72, 244-255 (2006). 3 Hoare, S.R. et al. Mechanism of corticotropin-releasing factor type I receptor regulation by nonpeptide antagonists. Mol Pharmacol. 63, 751-765 (2003). 4 He, L. et al. 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2, 4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: a potent, orally bioavailable CRF(1) . J. Med. Chem. 43, 449-456 (2000). 5Griebel, G. et al. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4- methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders. J. Pharmacol. Exp. Ther. 301, 333-345 (2002). 6Gully, D. et al. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5- methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization. J. Pharmacol. Exp. Ther. 301, 322-332 (2002). 7 Gilligan, P.J. et al. The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1 ,5- a]-pyrimidine: a corticotropin-releasing factor (hCRF1) antagonist. Bioorg. Med. Chem. 8, 181-199 (2000). 8 Hoare, S.R. Allosteric modulators of class B G-protein-coupled receptors. Curr. Neuropharmacol. 5, 168-179 (2007). 9Chen, C. et al. Design of 2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5- a]pyrimidine (NBI 30775/R121919) and structure--activity relationships of a series of potent and orally active corticotropin-releasing factor receptor antagonists. J. Med. Chem. 47, 4787-4798 (2004). 10 Salvatore, C.A. et al. Identification and pharmacological characterization of domains involved in binding of CGRP receptor antagonists to the calcitonin-like receptor. Biochemistry. 45, 1881-1887 (2006). 11 Petersen et al. Effects of a novel antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia. 44, 2018-2024 (2001). 12 Latsis, T. et al. Diverse effects of two allosteric inhibitors on the phosphorylation state of glycogen phosphorylase in hepatocytes. Biochem J. 368, 309-316 (2002). 13 Koole, C. et al. Allosteric ligands of the glucagon-like peptide 1 receptor (GLP-1R) differentially modulate endogenous and exogenous peptide responses in a pathway-selective manner: implications for drug screening. Mol. Pharmacol. 78, 456-465 (2010). 14 Koole, C. et al. Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation. Mol Pharmacol. 80, 486-497 (2011). 15Morris, L.C. et al. A duplexed High-Throughput Screen to identify allosteric modulators of the glucagon-like peptide 1 and glucagon receptors. J. Biomol. Screen. 19, 847-858 (2014).

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