More than four decades ago,1α,25(OH)2D3 was discovered and it is now recognized to be the most active hormonal form of vitamin D. Following this seminal discovery, several naturalmetabolites of 1α,25(OH)2D3 were also identified and it has been the general belief in the vitamin D scientific community that these natural metabolites formed during the process of inactivation of 1α,25(OH)2D3 are only inactive metabolites with no biological significance.
On the contrary, in my laboratory, we believe that various biological activities produced by the hormone 1α,25(OH)2D3 represent a combination of the actions generated not only by the hormone but also by its many natural daughter metabolites. During the past several years, we evaluated carefully the biological activities of various natural metabolites of 1α,25(OH)2D3 and its synthetic analogs. To our surprise, we discovered that some of the natural metabolites, especially with 24-oxo and 3-epimodifications have unique biological activities.
However, the same natural metabolites, unlike 1α,25(OH)2D3 were found to be less toxic. Basing on these findings, we developed new strategies to synthesize unique vitamin D analogs with 24-oxo and 3-epimodifications which appear to have great potential to become novel drugs in the future. The historical development of above concepts in my laboratory over a period of three decades will be discussed in the lecture.