Non-Hypercalcemic Vitamin D Analogues
Developed by: Instituto de Investigación Sanitaria Galicia Sur
The 1,25-dihydroxy vitamin D (1,25D) exerts its biological effects through binding to a specific intracellular receptor (Vitamin D Receptor, VDR) present in target cells. Numerous studies have demonstrated that 1,25D plays a major role in maintaining calcium/phosphate homeostasis. In addition, it regulates other physiological and pathological processes, including cell proliferation and differentiation. Nevertheless, its use in therapy is limited because of its hypercalcemic side effects. Given that Vitamin D inhibits proliferation and increases cell differentiation, the use of non-hypercalcemic Vitamin D analogues could be a therapeutic alternative in cancer and hyperproliferative disorders such as psoriasis, for which there is no oral treatment.
This technology describes the synthesis of new compounds with a certain affinity for the Vitamin D receptor, and that are active similarly to 1,25D, with the advantage of presenting a lower level of hypercalcemia or zero hypercalcemia.
Based on previous in vitro and in vivo tests, the best candidate of this family of compounds, PG-136, is a potent anti-proliferative drug without hypercalcemic activity. Besides, PG-136 shows anti-tumoral activity in human breast cancer cells and mouse xenograft tumor models.