Takahashi Tadakatsu, Morikawa Kazumi
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd. 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Curr Top Med Chem. 2006;6(12):1303-16. doi: 10.2174/156802606777864917.
1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an important hormone that regulates metabolism of calcium and phosphorus in small intestine, kidney, and bone, and its physiological action is expressed as ligand-dependent transcription activity mediated by vitamin D receptor (VDR). The VDR is found in various organs and cells including small intestine, kidney, and bone. In addition to the regulation of calcium metabolism, 1,25(OH)2D3 is involved in various biological reactions such as differentiation induction, antiproliferative effect, immunomodulatory effect, and regulation of cytokine and parathyroid hormone secretion. Thus, 1,25(OH)2D3 is expected to become a therapeutic drug for various related diseases. At present, a number of vitamin D derivatives are clinically applied to psoriasis, secondary hyperparathyroidism and osteoporosis but hypercalcemia and hypercalciuria are major concerns. Therefore, the current focus is directed toward new vitamin D derivatives with weak calcemic effects and a wide therapeutic window. In this summary, recent developments of new vitamin D derivatives for application in clinical treatment are described.
1α,25-二羟基维生素D3（1,25(OH)2D3）是一种重要的激素，可调节小肠、肾脏和骨骼中钙和磷的代谢，其生理作用表现为维生素D受体（VDR）介导的配体依赖性转录活性。VDR存在于包括小肠、肾脏和骨骼在内的各种器官和细胞中。除了调节钙代谢外，1,25(OH)2D3还参与各种生物反应，如诱导分化、抗增殖作用、免疫调节作用以及细胞因子和甲状旁腺激素分泌的调节。因此，1,25(OH)2D3有望成为治疗各种相关疾病的药物。目前，多种维生素D衍生物已在临床上应用于银屑病、继发性甲状旁腺功能亢进和骨质疏松症，但高钙血症和高钙尿症是主要关注点。因此，当前的重点是开发具有较弱血钙升高作用和较宽治疗窗的新型维生素D衍生物。在本综述中，描述了用于临床治疗的新型维生素D衍生物的最新进展。
