Table 1.
Control screening of known NR ligands
| Ligand | Activity | Score 1 | Score 2 | Score 3 | Score 4 | Selected | Binding | References |
|---|---|---|---|---|---|---|---|---|
| First series | ||||||||
| AGN193836 | RAR_agonist | −19.9 | −9.04 | −20.6 | −19.7 | − | + | (33) |
| ATRA | RAR pan-agonist | −46.4 | −41 | −41.7 | −41. | + | + | (34) |
| Ro415253 | RAR_antagonist | −25.5 | −22. | −28.3 | −28.6 | − | + | (28) |
| MX781 | RAR antagonist | −28. | −23.9 | −27.1 | −36.4 | + | + | (2) |
| CD2366 | RAR pan-antagonist | −28.5 | −23.3 | −30.9 | −32.3 | + | + | (34) |
| Targretin | RXR pan-agonist | −17.9 | −18.1 | −19.1 | −18.6 | − | − | (4) |
| SR11203 | RXR pan-agonist | −27.5 | −27. | −27. | −27.2 | − | − | (34) |
| Tamoxifen | ER modulator | −29.3 | −27.5 | −29.8 | −28.3 | − | − | (23) |
| Raloxifene | ER modulator | −23.4 | −20.8 | −26.7 | −34.6 | + | − | (22) |
| RU486 | Progest Rec antag. | −21.2 | −21.3 | −21.4 | −21.3 | − | − | (25) |
| 9cisRA | RAR/RXR agonist | −32.5 | −32.6 | −32.9 | −16.9 | + | + | (34) |
| AGN193109 | RAR pan-antagonist | −39.2 | −56. | −57.4 | −39.4 | + | + | (29) |
| AGNpartia | RAR partial agonist | −54.4 | −54.3 | −49.5 | −29.1 | + | + | (29) |
| Am580 | RAR_agonist | −34.2 | −34.4 | −34.8 | −34.5 | + | + | (34) |
| EM652 | ER antagonist | −27. | −27.4 | −21.7 | −28.8 | − | − | (35) |
| Antagonist 1 | Novel RAR antag. | −28.5 | −28.1 | −28.7 | −28.8 | − | + | (35) |
| Antagonist 2 | Novel RAR antag. | −27.6 | −38.9 | −40.2 | −26.3 | + | + | (35) |
| Second series | ||||||||
| AGN193836 | RAR_agonist | −37.2 | −36.5 | −36.7 | −35.3 | + | + | (33) |
| ATRA | RAR pan-agonist | −51.7 | −52.6 | −51.8 | −52.0 | + | + | (34) |
| Ro415253 | RAR_antagonist | −28.9 | −24.4 | −39.0 | −46.6 | + | + | (28) |
| MX781 | RAR antagonist | −45.3 | −48.0 | −40.2 | −45.6 | + | + | (2) |
| CD2366 | RAR pan-antagonist | −50.7 | −50.8 | −29.3 | −29.3 | + | + | (34) |
| Targretin | RXR pan-agonist | −25.4 | −23.0 | −22.2 | −31.0 | − | − | (4) |
| SR11203 | RXR pan-agonist | −28.2 | −22.7 | −22.1 | −27.5 | − | − | (34) |
| Tamoxifen | ER modulator | −26.4 | −24.6 | −30.3 | −23.4 | − | − | (23) |
| Raloxifene | ER modulator | −15.6 | −23.7 | −18.4 | −17.4 | − | − | (22) |
| RU486 | Progest Rec antag. | −21.4 | −20.6 | −20.3 | −20.1 | − | − | (25) |
| 9cisRA | RAR/RXR agonist | −38.8 | −39.5 | −33.5 | −38.7 | + | + | (34) |
| AGN193109 | RAR pan-antagonist | −55.1 | −55.5 | −41.2 | −54.8 | + | + | (29) |
| AGNpartia | RAR partial agonist | −61.4 | −61.3 | −61.4 | −61.0 | + | + | (29) |
| Am580 | RAR_agonist | −46.6 | −47.2 | −46.6 | −46.5 | + | + | (34) |
| EM652 | ER antagonist | −26.3 | −23.1 | −23.7 | −27.3 | − | − | (35) |
| Antagonist 1 | Novel RAR antag. | −32.1 | −32.1 | −31.7 | −31.6 | + | + | (35) |
| Antagonist 2 | Novel RAR antag. | −33.3 | −29.7 | −33.8 | −33.8 | + | + | (35) |
First series: A similar screening as the one performed on the ACD database was carried out four times on a small database made of known RAR antagonists, agonists, as well as ligands for other NRs and the two novel RAR antagonists. The ligands that met at least once with the criteria for selection used during the ACD screening are listed as Selected. The ligands that are experimentally binding to RAR are listed as Binding. Second series: Screening of known ligands after adjustment of the receptor's binding pocket conformation. The RAR antagonist Ro415253 was docked into our model of antagonist-bound RAR with flexible receptor side chains and ligand. The resulting receptor conformation was used for a novel screening.