TABLE 1

The binding affinities and functional potencies of compounds identified by virtual screening

Highlighted in bold are binding affinities and potencies in the submicromolar range, and ligand efficiencies 0.3 and higher.

Compound	VLS Model of D3R	pK_i^{^a}	LE^{^b}	pIC₅₀^{^c}		Fold IC₅₀	Tanimoto Distance^{^d}
Compound	VLS Model of D3R	D3R-Sf9	LE^{^b}	D3R-CHO	D2R-CHO	D3R vs. D2R	Tanimoto Distance^{^d}
6	APO	7.12 ± 0.08	0.33	ND	5.36 ± 0.14	—	0.33
7	APO	6.45 ± 0.04	0.29	8.18 ± 0.03	7.40 ± 0.13	6	0.41
12	APO	6.48 ± 0.14	0.30	5.70 ± 0.61	5.29 ± 0.63	2.5	0.29
16	APO	6.61 ± 0.17	0.31	7.29 ± 0.2	6.34 ± 0.09	10	0.34
19	APO	6.27 ± 0.10	0.33	6.66 ± 0.15	6.30 ± 0.14	2.5	0.11
20	APO	5.84 ± 0.17	0.28	5.72 ± 0.40	5.54 ± 0.05	1.5	0.27
21	APO	5.85 ± 0.18	0.25	4.90 ± 0.05	4.95 ± 0.08	2	0.41
24	APO	6.31 ± 0.14	0.29	6.86 ± 0.25	6.34 ± 0.16	3	0.48
25	APO	6.27 ± 0.08	0.30	5.85 ± 0.21	5.20 ± 0.11	4	0.40
27	APO	5.75 ± 0.02	0.27	5.32 ± 0.04	5.08 ± 0.06	2	0.31
28	APO	6.18 ± 0.28	0.26	6.19 ± 0.12	5.48 ± 0.20	5	0.44
29	APO	6.47 ± 0.04	0.33	5.86 ± 0.17	6.02 ± 0.01	0.7	0.34
34	APO	5.42 ± 0.13	0.25	5.45 ± 0.11	5.15 ± 0.27	6	0.36
53	APO	6.02 ± 0.12	0.31	4.63 ± 0.37	ND	—	0.25
8	Dopa	6.26 ± 0.46	0.27	4.87 ± 0.03	ND	>5	0.37
10	Dopa	5.11 ± 0.11	0.22	ND	ND^{^e}		0.39
23	Dopa	5.91 ± 0.07	0.45	6.24 ± 0.27	5.45 ± 0.14	6	0.52
26	Dopa	5.92 ± 0.12	0.25	6.31 ± 0.26	5.59 ± 0.11	5	0.41
32	Dopa	6.32 ± 0.17	0.41	6.38 ± 0.3	6.04 ± 0.14	3	0.5
33	Dopa	5.56 ± 0.07	0.30	5.44 ± 0.25	5.06 ± 0.15	2	0.39
39	Dopa	6.52 ± 0.21	0.35	5.01 ± 0.6^{^e}	ND	—	0.35
55	Dopa	5.89 ± 0.27	0.39	ND	ND	—	0.35

ND, no inhibition of 10 nM dopamine detected.
↵^a Binding affinities, as determined in a radioligand binding assay (see Fig. 7).
↵^b Ligand efficiency, kcal/mol per heavy atom.
↵^c Functional potencies, as ability to modulate the effect of 10 nM dopamine in an ERK1/2 phosphorylation assay (see Fig. 8).
↵^d Tanimoto distance to known dopamine receptor ligands (details shown in Supplemental Table 3).
↵^e Modest increase in dopamine-induced pERK1/2 phosphorylation.