Generation and Selection of Novel Estrogen Receptor Ligands Using the De Novo Structure-Based Design Tool, SkelGen
Stuart Firth‐Clark, Henriëtte M. G. Willems, Anthony A. Williams, William R. Harris · Journal of Chemical Information and Modeling · 2005
A de novo design approach to generating novel estrogen receptor (ER) ligands is described. The SkelGen program was used to generate ligands in the active sites of seven crystal structures of ERalpha. Seventeen high-scoring, diverse structures were selected from the SkelGen output and synthesized without introducing any modifications to the structures. Five ligands, four of which are novel, showed < or = 25 microM affinity, with the best compound displaying an IC50 of 340 nM. SkelGen can, therefore, be a powerful tool for designing active molecules.