Synthesis, metabolism, and biological activity of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

Synthetic Chemical Probes That Dissect Vitamin D Activities

“…3A). The ability of these six molecules [32][33][34] to activate VDR was next examined by a VDR-responsive reporter assay (Fig. 3B).…”

“…In our effort to delineate VD 3 activity, we initially searched for VD 3 analogs that activate VDR but lack SREBP inhibitory activity. An in-house library of 250 vitamin D congeners − was screened for their ability to inhibit the activity of an SREBP-responsive luciferase reporter, in which expression of luciferase is controlled by three SREBP binding sites. We found that a series of vitamin D analogs, bearing alkyltriazole and alkyltetrazole substituents at C2 ( 4 – 9 ) (Figure ), displayed limited SREBP inhibitory activities (Figure A).…”

“…We found that a series of vitamin D analogs, bearing alkyltriazole and alkyltetrazole substituents at C2 ( 4 – 9 ) (Figure ), displayed limited SREBP inhibitory activities (Figure A). The ability of these six molecules − to activate VDR was next examined by a VDR-responsive reporter assay (Figure B) . Comparison of the relative activities of the six compounds allowed us to select 2αC3Tet1 ( 6 ) as the VDR-selective activator.…”

Synthesis of the CYP24A1 major metabolite of 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D 3

“…The reaction was carried out in the reconstituted system containing recombinant rCYP24A1, bovine adrenodoxin (ADX), bovine NADPH-adrenodoxin reductase (ADR), NADPH, and AH-1 using the same methods as in our previous study [7]. After 30 min incubation, the metabolites were extracted and analyzed by reversed-phase HPLC as described in our previous study [7]. Fig.…”

Development of In Vitro and In Vivo Evaluation Systems for Vitamin D Derivatives and Their Application to Drug Discovery

“…We have demonstrated that the E. coli expression system is quite useful to investigate enzymatic properties of CYP24A1. Using this E. coli expression system, we have determined kinetic parameters of CYP24A1 in the metabolism of the native vitamin D and various vitamin D derivatives, and revealed their metabolic pathways [45][46][47][48][49][50][51][52][53][54][55][56][57][58]. CYP24A1 plays central roles in vitamin D metabolism and produces a wide variety of metabolites.…”