Background:

EC50: 325 nM

22(R)-hydroxy cholesterol is an endogenous agonist for liver X receptors (LXRs).

The liver X receptors, LXRR and LXRα, together with the farnesoid X receptor, FXR, form a subfamily of these orphan receptors. Recently, it has been reported that LXR and FXR are hormone receptors for oxysterols and bile acids, respectively.

In vitro: Previous study found that 22(R)-hydroxycholesterol was only found in the adrenals as an intermediate in pregnenolone biosynthesis, not similar with 24(R), 25-epoxycholesterol and 20(S)-hydroxycholesterol. In addition, the hydroxyl groups of 22(R)-hydroxycholesterol as well as its analogs of 23(S)-hydroxycholesterol and 24(S)-hydroxycholesterol would all lie between 2.0-2.5 from Trp443 [1]. In another study, the ABC1 mRNA expression could be induced in an additive fashion by 22(R)-hydroxycholesterol and 9-cis-retinoic acid in cultured macrophages, indicating induction by nuclear hormone receptors of the liver X receptor and retinoid X receptor family. Moreover, the upstream promoter was induced 7-fold by the treatment of 22(R)-hydroxycholesterol when transfected into RAW macrophages [2].

In vivo: So far, there is no animal in vivo data reported.

Clinical trial: Up to now, 22(R)-hydroxy cholesterol is still in the preclinical development stage.

参考文献:
[1] T.  A. Spencer, L. Dansu, J. S. Russel, et al. Pharmacophore analysis of the nuclear oxysterol receptor LXRα. Journal of Medicinal Chemistry 44, 886-897(2001).
[2] Costet P, Luo Y, Wang N, Tall AR.  Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem. 2000 Sep 8;275(36):28240-5.