Extended Data Table 2 |. 36 of the highest-affinity direct docking hits for D4 dopamine receptor.
See Supplementary Table 4 for all 549 compounds tested. See Supplementary Table 6 for novelty.
| ZINC ID | Cluster Rank* | TC† | CAMP EC50 (nM) | Gi BRET EC50 (nM) | Tango EC50 (nM) | Arrestin BRET EC50 (nM) | Bias Factor | Ki (nM) | ||
|---|---|---|---|---|---|---|---|---|---|---|
| D4 | D2 | D3 | ||||||||
| ZINC621433144 | 611 | 0.33 | 0.18 | 0.56 | 57.3 | 2.3 | 17 to G protein | 4.30 | >10,000 | >10,000 |
| ZINC621433143 (diastereomeric mixture) | 611 | 0.33 | 2.3 | 22.8 | 74.1 | 13.03 | 1 | 18 | >10,000 | >10,000 |
| ZINC361131264 | 611 | 0.33 | 7.3 | 21.93 | 151 | 890.1 | 26 to G protein | 72 | >10,000 | >10,000 |
| ZINC361131265 | 611 | 0.33 | 59 | 1,778 | 556 | ND‡ | 11 to G protein | 185 | >10,000 | >10,000 |
| ZINC621433143 | 611 | 0.33 | 350 | 3,148 | 898 | 1,246 | 7 to Arrestin | 669 | >10,000 | >10,000 |
| ZINC464771011 | 937 | 0.32 | 10.4 | NT§ | 1,141 | NT | 3 to Arrestin | 140 | >10,000 | >10,000 |
| ZINC270269326 | 1,510 | 0.32 | 17 | 11.7 | 172.3 | NT | 2 to Arrestin | 500 | >10,000 | >10,000 |
| ZINC465129598 | 1,565 | 0.32 | 24 | 22.9 | 210.1 | NT | 2 to Arrestin | 80 | >10,000 | >10,000 |
| ZINC278933042 | 5,796 | 0.27 | 41 | NT | 22,340 | NT | NT | 270 | >10,000 | >10,000 |
| ZINC293543779 | 420 | 0.31 | 130 | NT | 1,684 | NT | 1 | 1200 | >10,000 | >10,000 |
| ZINC466408491 | 274 | 0.27 | 270 | NT | 8,529 | NT | 4 to Arrestin | 3,900 | 4,780 | 5,430 |
| ZINC567992445 | 5,854 | 0.33 | 4,820 | NT | NT | NT | NT | 850 | >10,000 | >10,000 |
| ZINC413570733 | 81,969 | 0.28 | IC50 = 5,900 | NT | NT | NT | NT | 130 | >10,000 | >10,000 |
| ZINC155719879 | 132 | 0.31 | 7,200 | NT | NT | NT | NT | 460 | >10,000 | >10,000 |
| ZINC569686370 | 17,659 | 0.34 | 7,800 | NT | NT | NT | NT | 550 | >10,000 | >10,000 |
| ZINC268141382 | 734 | 0.3 | 9,900 | NT | NT | NT | NT | 560 | >10,000 | >10,000 |
| ZINC127859549 | 42,379 | 0.33 | 10,400 | NT | NT | NT | NT | 260 | >10,000 | 3,570 |
| ZINC437075156 | 1,542 | 0.34 | 10,400 | NT | NT | NT | NT | 190 | >10,000 | >10,000 |
| ZINC130532671 | 89 | 0.3 | IC50 = 10,800 | NT | NT | NT | NT | 320 | >10,000 | >10,000 |
| ZINC518842964 | 1,631 | 0.33 | 22,100 | NT | NT | NT | NT | 120 | >10,000 | >10,000 |
| ZINC651262870 | 1,328 | 0.32 | 31,000 | NT | NT | NT | NT | 440 | >10,000 | >10,000 |
| ZINC609076791 | 572 | 0.33 | 31,500 | NT | NT | NT | NT | 330 | >10,000 | >10,000 |
| ZINC362128724 | 1,615 | 0.34 | 32,200 | NT | NT | NT | NT | 160 | 8,610 | 6,040 |
| ZINC467716766 | 1,171 | 0.31 | 34,800 | NT | NT | NT | NT | 700 | >10,000 | >10,000 |
| ZINC375299581 | 198 | 0.32 | ND | NT | NT | NT | NT | 180 | >10,000 | >10,000 |
| ZINC247398558 | 225 | 0.35 | ND | NT | NT | NT | NT | 210 | >10,000 | >10,000 |
| ZINC176752603 | 92 | 0.3 | ND | NT | NT | NT | NT | 300 | >10,000 | >10,000 |
| ZINC480408888 | 75 | 0.34 | ND | NT | NT | NT | NT | 400 | >10,000 | >10,000 |
| ZINC449156693 | 5,802 | 0.28 | ND | NT | NT | NT | NT | 760 | >10,000 | >10,000 |
| ZINC640028109 | 255 | 0.29 | ND | NT | NT | NT | NT | 810 | >10,000 | >10,000 |
| ZINC92642352 | 42,403 | 0.23 | ND | NT | NT | NT | NT | 820 | >10,000 | >10,000 |
| ZINC572302473 | 577 | 0.29 | ND | NT | NT | NT | NT | 910 | >10,000 | >10,000 |
| ZINC601953994 | 235 | 0.32 | ND | NT | NT | NT | NT | 980 | >10,000 | >10,000 |
| ZINC615622500 | 204 | 0.34 | ND | NT | 3,074 | NT | ND | 150 | >10,000 | 5,400 |
| ZINC358506216 | 5,857 | 0.33 | NT | NT | NT | NT | NT | 250 | 5,880 | 6,540 |
| ZINC415558697 | 17,674 | 0.27 | NT | NT | NT | NT | NT | 990 | 2,000 | 5,870 |
| ZINC237938360 | 17,654 | 0.32 | NT | NT | NT | NT | NT | 180 | 5,720 | 1,070 |
| Quinpirole | ND | ND | 0.32 | 1.82 | 63.3 | NT | 1 | 14.2 | ND | ND |
| Dopamine | ND | ND | 0.65 | 0.91 | 79.4 | NT | 2 to G protein | 6.30 | ND | ND |
*
Cluster Rank: position in cluster head (see Methods) list sorted by DOCK score;
†
TC: Tanimoto Coefficient to dopaminergic, serotonergic, or adrenergic knowns from ChEMBL;
‡
Not determined, ND. The compound was tested but no measurable value was observed.
§
Not Tested, NT