Zymostenol

Zymostenol is a late-stage precursor in the biosynthesis of cholesterol.¹ It is an agonist of retinoic acid receptor-related orphan receptor γ (RORγ) with an EC₅₀ value of 1 µM in a RORγ coactivator recruitment assay in the presence of ursolic acid (Item No. 10072). It increases the number of myelin basic protein-positive oligodendrocytes generated from oligodendrocyte precursor cells in vitro.² Zymostenol accumulates in cells following administration of microsomal antiestrogen-binding site (AEBS) ligands, such as tamoxifen (Item No. 13258), which are associated with cell differentiation and a protective type of autophagy.^3,4 When used alone at a concentration of 20 µM, zymostenol halts the cell cycle at the G₀/G₁ phase and increases the levels of free sterols, esterified sterols, and triacylglycerols in MCF-7 cells.³

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1. Hu, X., Wang, Y., Hao, L.-Y., et al. Sterol metabolism controls T_H17 differentiation by generating endogenous RORγ agonists. Nat. Chem. Biol. 11(9), 141-147 (2015).

2. Hubler, Z., Allimuthu, D., Bederman, I., et al. Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature 560(7718), 372-376 (2018).

3. Payré, B., de Medina, P., Boubekeur, N., et al. Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human breast cancer cells through the modulation of cholesterol metabolism. Mol. Cancer Ther. 7(12), 3707-3718 (2008).

4. Poirot, M., and Silvente-Poirot, S. The tumor-suppressor cholesterol metabolite, dendrogenin A, is a new class of LXR modulator activating lethal autophagy in cancers. Biochem. Pharmacol. 153, 75-81 (2018).