Table 1. Hit compounds from VLS with G_i/o mediated potency EC₅₀ <1 µM for at least one MT receptor.

	MT1					MT2					MT2/MT1
Compound	pKi ± SEM*	pEC50 ± SEM	EC50(nM)	Emax† ± SEM	LE‡c	pKi ± SEM	pEC50 ± SEM	EC50(nM)	Emax ± SEM	LE	Selectivity§	Tanimoto¶
21	6.31 ± 0.11	7.91 ± 0.05	12.0	93.8 ± 2.5	0.69	6.91 ± 0.05	9.44 ± 0.08	0.36	86.1 ± 3.2	0.83	30.6	0.50
23	5.42 ± 0.03	7.16 ± 0.09	57.5	96.9 ± 5.3	0.56	5.56 ± 0.13	7.69 ± 0.08	20.42	91.7 ± 3.0	0.60	2.7	0.22
28	7.78 ± 0.10	10.39 ± 0.04	0.04	95.3 ± 2.6	0.86	7.63 ± 0.08	10.35 ± 0.10	0.04	69.4 ± 4.0	0.85	0.7	0.05
29	5.22 ± 0.07	6.83 ± 0.06	144.5	87.5 ± 4.5	0.53	5.61 ± 0.05	7.46 ± 0.10	34.67	69.4 ± 8.0	0.58	3.3	0.43
37	5.07 ± 0.13	ND	>30000	ND	ND	5.45 ± 0.10	6.85 ± 0.19	141.25	61.1 ± 9.1	0.53	>1000.0	0.57
44	4.19 ± 0.36	3.33 ± 0.36	57544.0	72.8 ± 4.7	0.33	4.95 ± 0.30	6.58 ± 0.13	263.03	88.9 ± 6.3	0.51	267.2	0.59
45	4.54 ± 0.15	5.06 ± 0.12	8709.6	90.6 ± 14.3	0.44	5.26 ± 0.19	6.37 ± 0.13	426.58	75.0 ± 7.4	0.56	16.9	0.59
47	4.58 ± 0.07	5.25 ± 0.16	2344.2	112.4 ± 5.2	0.46	5.91 ± 0.12	7.99 ± 0.10	10.23	91.7 ± 3.0	0.66	186.9	0.60
54	5.03 ± 0.06	6.06 ± 0.07	741.3	82.8 ± 4.3	0.54	5.56 ± 0.10	7.74 ± 0.10	18.20	75.0 ± 3.7	0.68	36.9	0.43
57	4.84 ± 0.03	5.72 ± 0.11	1778.3	87.5 ± 9.1	0.47	5.37 ± 0.04	6.88 ± 0.15	131.83	66.7 ± 8.3	0.57	10.3	0.53
62	4.32 ± 0.11	4.39 ± 0.42	42658.0	54.1 ± 10.0	0.36	5.49 ± 0.33	7.28 ± 0.14	52.48	58.3 ± 4.8	0.60	875.9	0.64
Melatonin	9.06 ± 0.14	11.38 ± 0.06	0.004	100.0 ± 5.6	0.93	9.27 ± 0.14	10.30 ± 0.14	0.05	100.0 ± 5.6	0.84	0.1	0.00

Standard error of the mean, N = 3.

^† Activation compared to melatonin.

 Ligand efficiency (based on EC₅₀).

^§Selectivity in folds (calculated as: Antilog (log(E_max/EC₅₀) MT₂- log (E_max/EC₅₀) MT₁)). MT₁ selectivity is shown as underlined values.

^¶ Tanimoto distance from closest MT receptor ligands in ChEMBL database with pAct >6. Hits with EC₅₀ <100 nM are displayed in bold, and with E_max <70% in italic.