History of the development of new vitamin D analogs: studies on 22-oxacalcitriol (OCT) and 2beta-(3-hydroxypropoxy)calcitriol (ED-71).
In 1981 Suda and his colleagues first reported the new activity of calcitriol namely its ability to differentiate the myeloid leukemia cells into normal monocytes-macrophages. However, the possibility of using calcitriol as an antileukemic drug was not feasible because of its potent calcemic effects. Based on these observations, several pharmaceutical companies 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. As a result, numerous noncalcemic analogs with a potential for the treatment of leukemia and other cancers were synthesized. The group at Chugai introduced two characteristic analogs of opposite type namely, 22-oxacalcitriol (OCT) and 2beta-(3-hydroxypropoxy)calcitriol (ED-71) which have been shown to have therapeutic value and are already being used clinically. The work on OCT and ED-71 together with the work on calcipotriol and KH-1060 by Leo Laboratories, and 1alpha,25(OH)(2)-16-ene-23-yne-D(3) by Hoffmann-La Roche, vigorously stimulated research world-wide in the development of vitamin D analogs into pharmaceutical products. More recently new impressive vitamin D analogs such as 3-epi analogs, 19-nor analogs, 18-nor analogs, 2-methyl-20-epi-calcitriol, non-steroidal vitamin D analogs are being developed. The authors are convinced that various vitamin D analogs will become highly effective therapeutic agents at the clinical level in the new century, and also that a new theory on the mechanism of vitamin D action will be generated.
Nishii
Y
Y
Medical Culture Inc., Toshima-ku, Tokyo, Japan. Nishiiysh-mc@chugai-pharm.co.jp
Okano
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000266:history / Q000627:therapeutic use; D002117:Calcitriol / Q000031:analogs & derivatives / Q000266:history* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy / Q000266:history; D014807:Vitamin D / Q000031:analogs & derivatives / Q000266:history / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014807:Vitamin D; D002117:Calcitriol; C547512:eldecalcitol; C051883:maxacalcitol