Structure of the ligand-binding domain of rat VDR in complex with the nonsecosteroidal vitamin D3 analogue YR301.

ABSTRACT: Vitamin D receptor (VDR) is a ligand-inducible hormone receptor that mediates 1alpha,25(OH)(2)D(3) action, regulating calcium and phosphate metabolism, induces potent cell differentiation activity and has immunosuppressive effects. Analogues of 1alpha,25(OH)(2)D(3) have been used clinically for some years. However, the risk of potential side effects limits the use of these substances. LG190178 is a novel nonsecosteroidal ligand for VDR. (2S)-3-[4-(3-{4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl}pentan-3-yl)-2-methylphenoxy] propane-1,2-diol (YR301) is the only one of the four evaluated stereoisomers of LG190178 to have strong activity. To understand the strong activity of YR301, the crystal structure of YR301 complexed with the rat VDR ligand-binding domain (VDR LBD) was solved at

SUBMITTER: Kakuda S 

PROVIDER: S-EPMC2581693 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature