TABLE 1.
Transcriptional activities of hRARα challenged with natural or synthetic retinoidsa
| Ligand | Biological activity | Kd (RAR; nM) | EC50 (RAR/RXR; nM) | Relative potency (RAR/RXR; %) |
|---|---|---|---|---|
| atRA | RARα, -β, and -γ agonist | 3.3 | 10.80 | 100 |
| 9-cis RA | Panagonist | 7.1 | 18.80 | 187.8 |
| TTNPB | RARα, -β, and -γ agonist | 2.2 | 1.05 | 90.2 |
| CD367 | RARα, -β, and -γ agonist | 4.0 | 0.91 | 55.0 |
| Am580 | RARα agonist | 8.1 | 0.74 | 72.5 |
| CD3106 | RARα, -β, and -γ antagonist | 20.0 | ND | 0 |
| CD2425 | RXRα, -β, and -γ agonist | >10,000 | 10 | 15 |
The main features of each ligand (biological activity in transient transfection assays and selectivity; Kd for hRARα) are indicated. In all cases but one, Kd values were obtained as described in reference 27; data for CD3106 were taken from reference 20. HeLa cells were transfected with hRARα and hRXRα expression vectors and the TREpal-TATA Luc reporter gene. The TREpal sequence is cggtagAGGTCATGACCTctcg (26). EC50 and relative potency values were deduced from dose-response curves in which the y axis represented the average luciferase activity (expressed as the percentage of the response observed in the presence of 1 μM atRA; n = 6 from eight independent experiments), and the x axis represented concentrations of ligand. Relative potency values represent the maximal luciferase activity observed with the tested ligand relative to that observed in the presence of 1 μM atRA. EC50s represent the ligand concentration yielding half-maximal luciferase activity. Standard errors never exceeded 8%. Chemical names of retinoids: CD367, 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid; TTNPB, (E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propen-1-y1]benzoic acid; Am580, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid; CD2425 (AGN 190701), ((E)-2-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)propen-1-yl]-4-thiophenecarboxylic acid. ND, not determined.