The active form of vitamin D
3, 1α,25-dihydroxyvitamin D
3 1, is not only a regulator of calcium homeostasis and bone development and remodeling but also a potent differentiator of leukemic cells. LG190178 is a novel non-secostreroidal ligand for vitamin D receptor (VDR), which may have potential as therapeutics for cancer, leukemia and psoriasis with less calcium mobilization side effects than are associated with secosteroidal 1α,25-(OH)
2D
3 analogs. But LG190178 includes 4 stereoisomers. We calculated to make ducking model of 4 isomers and VDR, respectively. (S,S)-Isomer model is most stable one. There are hydrogen bonds between 2-OH and Arg-274, Ser-237 and between 2'-OH and His-305, His-397. (2S)-Isomers ((S,S) and (S,R)) are more important than (2R)-isomers. We synthesized (2S)- and (2R)-LG190178.
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