ZK168281 是一种 1α,25(OH)2D3 类似物，也是一种纯 VDR 拮抗剂，Kd 值为 0.1 nM。ZK168281 是其受体 CoA 相互作用的有效抑制剂。
ZK168281 is a 25-carboxylic ester 1α,25(OH)2D3 analog and a pure VDR antagonist with a Kd value of 0.1 nM. ZK168281 is an effective inhibitor of the coactivator (CoA) interaction of its receptor[1].
ZK168281 resembles more the mouse constitutive androstane receptor (CAR) inverse agonist Androstanol in its ability to recruit corepressor (CoR) proteins. A salt bridge between the CoR and a conserved lysine in helix 4 of the nuclear receptor (NR) is central to this interaction, but also helix 12 was stabilized by direct contacts with residues of the CoR. Fixation of helix 12 in the antagonistic/inverse agonistic conformation prevents an energetically unfavorable free floatation of the C terminus[1].
[1]. Lempi?inen H, et al. Antagonist- and inverse agonist-driven interactions of the vitamin D receptor and the constitutive androstane receptor with corepressor protein. Mol Endocrinol. 2005 Sep;19(9):2258-72.
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