(2)ビタミンD分化誘導作用の発見がもたらした創薬研究(シンポジウム:「脂溶性ビタミン研究の最前線」)

抄録

In 1981, Suda and colleagues reported the differentiation-inducing activities of calcitriol. Several companies and organic chemists initiated the synthesis of vitamin D analogs with the aim to separate the calcemic actions of calcitriol from its actions on regulating the cell growth and differentiation. The group of Chugai company succeeded in marketing OCT, Oxarol, as a therapeutic agent for secondary hyperparathyroidism and psoriasis, and Leo company, MC-903, Dovonex, as a drug for psoriasis. The work on OCT and MC-903 vigorously stimulated research world-wide in the development of vitamin D analogs into pharmaceutical products without inducing hypercalcemia. New many non-calcemic vitamin D analogs are being developed. D-hormone is widely accepted as being an antiresorptive drug in bone The anabolic effects of alfacalcidol were confirmed in vitamm-D repleted rats In bone, alfacalcidol, also calcitriol, acts independently of its effects on intestinal calcium absorption and the resultant suppression of PTH. The new vitamin D analogs, ED-71 and 2-MD, which had a potent effect on bone formation, markedly increased bone mass and bone strength in OVX rats When the biological properties of ED-71 and 2-MD were compared, big differences were observed. Judging from these observations, it is impossible to explain about the mechanism of bone formation by D-hormone analogs. Recently, another unexplamable reports appeared. In spite of no binding activities of 19-nor-OCT to the vitamin D receptor (VDR), it is able to induce 25-hydroxyvitamin D 24-hydroxylase depending on VDR Non-steroidal vitamin D analogs such as CD-483 and carborane analogs showed the vitamin D like biological activities. Examining about these results in vitamin D metabolites, and we should think about the criteria of vitamin D.