Assessment of the free binding energy of 1,25-dihydroxyvitamin D-3 and its analogs with the human VDR receptor model

作者：Kamel Karol^*; Kolinski Andrzej

来源：Acta Biochimica Polonica, 2012, 59(4): 653-660.

• vitamin D
• docking
• drug design
• KH 1060
• RO 25-9022
• ER 1089

1,25-dihydroxyvitamin D-3 has quite significant anticancer properties, but its strong calcemic effect in principle excludes it as a potential anticancer drug. Currently, a lot of effort is being devoted to develop potent anticancer analogs of 1,25-dihydroxyvitamin D-3 that would not induce hypercalcemia during therapy. In this work, the free binding energy of the VDR receptor with 1,25-dihydroxyvitamin D-3 and its three potent analogs (EB 1089, KH 1060 and RO 25-9022) is calculated and compared with each other. With this approach, we could estimate the relative binding affinity of the most potent analog, RO 25-9022, and also revealed a quite distinct mechanism of its interaction with VDR.

• 出版日期2012