Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226.
The androgen receptor (AR) is a ligand-inducible steroid hormone receptor that mediates androgen action, determining male sexual phenotypes and promoting spermatogenesis. As the androgens play a dominant role in male sexual development and function, steroidal androgen agonists have been used clinically for some years. However, there is a risk of potential side effects and most steroidal androgens cannot be dosed orally, which limits the use of these substances. 1,2-Dihydro-6-N,N-bis(2,2,2-trifluoroethyl)amino-4-trifluoromethyl-2-quinolinone (LGD2226) is a synthetic nonsteroidal ligand and a novel selective AR modulator. The crystal structure of the complex of LGD2226 with the androgen receptor ligand-binding domain (AR LBD) at 2.1 A was solved and compared with the structure of the AR LBD-R1881 complex. It is hoped that this will aid in further explaining the selectivity of LGD2226 observed in in vitro and in vivo assays and in developing more selective and effective therapeutic agents.
Wang
Feng
F
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, People's Republic of China.
Liu
Xiao-qin
XQ
Li
He
H
Liang
Kai-ni
KN
Miner
Jeffrey N
JN
Hong
Mei
M
Kallel
E Adam
EA
van Oeveren
Arjan
A
Zhi
Lin
L
Jiang
Tao
T
D001665:Binding Sites; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry
D008024:Ligands; D011944:Receptors, Androgen; D011994:Recombinant Proteins