| [ Summary ] |
A little over two decades ago, the vitamin D3 activation pathway was elucidated and alfacalcidol arrived on the scene as a prodrug for active vitamin D3, 1α, 25-dihydroxyvitamin D3, to remedy vitamin D3 deficiency. With the concurrent reported discovery of the differentiation-inducing effect of active vitamin D3, its diverse physiological effects have become appreciated and research aiming to accentuate selected physiological effects with analogue synthesis has produced new development. Our studies aimed particularly at separating the differentiation-inducing effect / cell growthinhibitory effect and the calcemic effect of active vitamin D3, which lead to the development of two characteristic analogues, 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 analogue, 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 the methodology for searching for the next-generation analogues, exemplified by the new analogue, DD-281, based on the knowledge accumulated through development of OCT and ED-71. |