Ligand structure-function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment).

Abstract

It has become readily apparent to many scientists and pharmaceutical companies that the vitamin D endocrine system offers a wide array of drug development opportunities. There are already successes, as noted by 1alpha,25(OH)2D3 (Roche, and Abbott) for renal osteodystrophy and osteoporosis and 1alpha(OH)D3 (Leo, Chugai, Teijin) for renal osteodystrophy and (in Japan) osteoporosis, 1alpha,24(OH)2-24-cyclopropyl-D3 (Dovonex) and 1alpha,24(OH)2D3 (Teijin) for psoriasis, and 19-nor-1alpha,25(OH)2D2 (Abbott) for renal osteodystrophy, as well as drugs under active development. Yet there are still many important and challenging drug development frontiers, particularly in the area of cancer treatment and immune system disorders where exploration is only in the initial early stages. In addition, the application of vitamin D-related drugs in neurology and brain pathology should not be overlooked. It is to be hoped that the cellular and molecular basis for the vexing problem of analog-induced hypercalcemia will be elucidated. Given that there are believed to be over 2000 analogs of 1alpha,25(OH)2D3 already available for consideration, it is to be expected that over the next decade a significant number of new vitamin D structure-function drug development projects will be brought to conclusion.