The development of a bone- and parathyroid-specific analog of vitamin D: 2-methylene-19-Nor-(20S)-1α,25-dihydroxyvitamin D3.

ABSTRACT: The goal of synthetic chemists in the vitamin D field has been to produce an analog(s) of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) that is selective for a specific function. The accumulation of structure/function information has led to the synthesis of two analogs that are both selective and more potent than 1,25-(OH)2D3, that is, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) and 2α-methyl-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2AMD). In vivo, the efficacy of 2MD is approximately equal to that of 1,25-(OH)2D3 in intestinal calcium transport but is 30- to 100-fold more active in bone mobilization. In vitro, 2MD supports new bone synthesis at 10(-12) M, whereas 1,25-(OH)2D3 is active at 10(-8) M. Similarly, 2MD is two orders of magnitude more potent than 1,25-(OH)2D3 in stimulati

SUBMITTER: Deluca HF 

PROVIDER: S-EPMC4015459 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature