This present disclosure is directed to novel prodrugs of activated vitamin D3 compounds. The prodrugs can be designed to have one or more beneficial properties, such as selective inhibition of the enzyme CYP24, low calcemic activity, and anti-proliferative activity. Specifically, these prodrugs are 1-deoxy prohormones of active Vitamin D analogs, e.g. analogs of calcitriol. This disclosure is also directed to pharmaceutical and diagnostic compositions containing the prodrugs of the invention, and to their medical use, particularly as prodrugs in the treatment and/or prevention of diseases.