National Center for
3RLJ: Crystal Structure Of The Androgen Receptor Ligand Binding Domain In Complex With Sarm S-22
Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets
J. Med. Chem. (2011) 54 p.3973-3976
Several new androgen receptor antagonists were synthesized and found to have varying activities across typically anti-androgen resistant mutants (Thr877 --> Ala and Trp741 --> Leu) and markedly improved potency over previously reported pan-antagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877 --> Ala) shows that the receptor can accommodate the added bulk presented by phenyl to naphthyl substitution, casting doubt on previous reports of predicted binding orientation and the causes of antagonism in bulky-B-ring antagonists.