History of the development of new vitamin D analogs: studies on 22-oxacalcitriol (OCT) and 2β-(3-hydroxypropoxy)calcitriol (ED-71)

• Published in: Steroids Vol. 66; no. 3; pp. 137 - 146
• Main Authors: Nishii, Y., Okano, T.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2001; Elsevier Science
• Subjects: 1α,25(OH) 2D 3; Biological and medical sciences; ED-71; General and cellular metabolism. Vitamins; KH-1060; MC-903; Medical sciences; OCT; Osteoporosis; Pharmacology. Drug treatments; Psoriasis; VDR; Vitamin D analogs; OCT; Osteoporosis; ED-71; Psoriasis; VDR; 1α,25(OH) 2D 3; KH-1060; Vitamin D analogs; MC-903; Vitamin D; Steroid hormone; Analog; Leukemia; Diseases of the osteoarticular system; Calcitriol; Malignant hemopathy; Bone disease; Review; Case history
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(00)00227-0

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 2β-(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 1α,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.