Vitamin D receptor exhibits different pharmacodynamic features in tumoral and normal microenvironments: A molecular modeling study.

RIBONE SR; FERRONATO MJ; VITALE C; FALL Y; CURINO AC; FACCHINETTI MM; QUEVEDO MA

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2020 vol. 200

0960-0760

he vitamin D receptor (VDR) constitutes a promising therapeutic target for the treatment of cancer.Unfortunately, its natural agonist calcitriol does not have clinical utility due to its potential to induce hypercalcemic effects at the concentrations required to display antitumoral activity. For this reason, the search for new calcitriol analogues with adequate therapeutic profiles has been actively pursued by the scientific community. We have previously reported the obtaining and the biological activity evaluation of new calcitriol analogues by modification of its sidechain, which exhibited relevant antiproliferative and selectivity profiles against tumoral and normal cells. In this work we conducted molecular modeling studies (i.e. molecular docking, molecular dynamics, constant pH molecular dynamics (CpHMD) and free energy of binding analysis) to elucidate at an atomistic level the molecular basis related to the potential of the new calcitriol analogues to achieve selectivity betwe