alexa Vitamin D receptor ligands: the impact of crystal structures.
Biomedical Sciences

Biomedical Sciences

Journal of Biomolecular Research & Therapeutics

Author(s): Carlberg C, Molnr F, Mourio A

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Abstract INTRODUCTION: In the past years, the biologically active form of vitamin D(3), 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)), has received large appreciation due to the broad physiological impact of the hormone and its nuclear receptor, the transcription factor vitamin D receptor (VDR). Recently, the understanding of VDR actions has progressed greatly, due to VDR crystal structures with various ligands. AREAS COVERED: This review will present and discuss new synthetic agonistic and antagonistic 1α,25(OH)(2)D(3) analogs in the context of the recent insights provided by VDR crystal structures. EXPERT OPINION: During the last 5 years, a large number of new 1α,25(OH)(2)D(3) analogs, many of which have an interesting functional profile, have been patented. Moreover, for a surprisingly high number of 1α,25(OH)(2)D(3) analogs, the crystal structure data of their complex with the VDR is available. This structural information provides important insight into the functional potential of the VDR ligands and explains their agonistic and antagonistic action. However, so far, only for a few VDR ligands, a rational design, based on crystal structure information, has been applied. The design of future analogs may also take the specificity of co-factor interaction into account, in order to create selective VDR modulators. This article was published in Expert Opin Ther Pat and referenced in Journal of Biomolecular Research & Therapeutics

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