[Progress in research on vitamin D analogs].
A little over two decades ago, the vitamin D activation pathway was elucidated and alfacalcidol arrived on the scene as a prodrug for active vitamin D, 1,25-dihydroxyvitamin D(3), to remedy vitamin D deficiency. With the concurrent reported discovery of the differentiation-inducing effect of active vitamin D, its diverse physiological effects have become appreciated and the research aiming to accentuate selected physiological effects by analog research has made a fresh development. Our studies aimed particularly at separating the differentiation-inducing effect/cell growth-inhibitory effect and the calcemic effect of active vitamin D led to the development of two characteristic analogs, OCT and ED-71. OCT, characterized by its profound differentiation-inducing effect and modest calcemic effect, is currently in practical use as an injectable therapeutic agent for secondary hyperparathyroidism as well as in clinical settings as an ointment for the treatment of psoriasis vulgaris. The other analog, ED-71, possesses a profile inverse to that of OCT and is now under clinical development as an oral preparation for treatment of osteoporosis. The present overview refers to methodology of searching next-generation analogs, exemplifying a new analog, DD-281, based on the knowledge accumulated through development of OCT and ED-71.
Kubodera
Noboru
N
Chugai Pharmaceutical Co., Ltd., Bone Disease Area Dept.
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004304:Dosage Forms; D015195:Drug Design; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy; D010024:Osteoporosis / Q000188:drug therapy; D011565:Psoriasis / Q000188:drug therapy; D018167:Receptors, Calcitriol / Q000502:physiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D004304:Dosage Forms; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002117:Calcitriol; C547512:eldecalcitol; C051883:maxacalcitol