Figure 8
From: Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist
Potential for exploiting the SS-RJW100 binding mode to generate LRH-1 antagonists. (a) Superposition the ligands (sticks) and AF-H (cartoon) from three structures: oestrogen receptor gamma in the active state (dark blue, from PBD 2GP7), bound to 4-hydroxy tamoxifen (4-OHT, pale green, from PDB 2GPU)45, and LRH-1-SS-RJW100 (grey). The clash of 4-OHT with residue L532 is shown. (b) A comparison of chemical structures of SS-RJW100, 4-OHT, and 30-endo (c) Docking of the compound 30-endo (dark blue sticks)33 in the SS-RJW100 structure as an example of how bulky groups could be added to the SS-RJW100 scaffold to extend toward the AF-H. The acetoxy moiety appended to the ligand bicyclic core at position 2 is within 3 Å of the AF-H and nearly overlaps with TAM. The blue circle indicates space that could accommodate bulk and displace the activation function helix (AF-H) in a similar manner to TAM.
