ZK159222, a 25-carboxylic ester analogue of 1α,25-(OH)2D3, is a potent 1α,25-(OH)2D3?receptor (VDR)?antagonist. The mechanism of ZK159222 antagonistic action is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators. ZK159222 has a partial agonistic character.In Vitro: ZK159222, displayed the profile of a weak VDR agonists that requires an approximate 7-fold higher concentration than of the natural hormone 1α,25-(OH)2D3?to stabilize VDR-RXR heterodimer complex formation on a DR3-type VDRE. ZK159222 was found to belong to the category of 1α,25-(OH)2D3?analogues that stabilize an additional third functional VDR conformation, which has also been described for some agonistic 20-epi analogues. The remaining reporter gene activity that was obtained by a combined treatment of 10 nM?1α,25-(OH)2D3 with 1 μM?ZK159222 is close to the partial agonistic activity of 1 μM?ZK159222.