PT  - JOURNAL ARTICLE
AU  - NATACHA ROCHEL
AU  - DINO MORAS
TI  - Crystal Structure of a Vitamin D<sub>3</sub> Analog, ZK203278, Showing Dissociated Profile
DP  - 2012 Jan 01
TA  - Anticancer Research
PG  - 335--339
VI  - 32
IP  - 1
4099  - http://ar.iiarjournals.org/content/32/1/335.short
4100  - http://ar.iiarjournals.org/content/32/1/335.full
SO  - Anticancer Res2012 Jan 01; 32
AB  - The plethora of actions of 1α,25-dihydroxyvitamin D3, the active form of the seco-steroid hormone vitamin D, in various systems suggested wide clinical applications in treatments for renal osteodystrophy, osteoporosis, psoriasis, cancer, autoimmune diseases and prevention of graft rejection. However, the major side-effects of hypercalcemia of VDR ligands limit their use. ZK203278, a novel synthetic analog has been shown to act as a potent immunomodulator and presents dissociated biologic profile with low calcemic side-effects. Here, we described the crystal structures of the hVDR ligand-binding domain in complex with ZK203278 and determined its correlation with its specific dissociated biologic profile. The VDR/ZK203278 structure, in comparison with VDR/1α,25-dihydroxyvitamin D3, shows specific interactions of the thiazole group of ZK203278 with residues of H3, H11 and H12. These specific interactions may lead to altered selective interactions with co-regulators and consequently to the dissociated biologic profile of this novel ligand.