Dendrogenin A (DDA) is a selective liver X receptor (LXR) modulator (SLiM), an inhibitor of cholesterol epoxide hydrolase (ChEH; Ki = 120 nM), and an active metabolite of cholesterol.^1,2 It is formed from 5,6α-epoxy cholesterol via conjugation with histamine by DDA synthase.^2,1,3 DDA is found in non-cancerous human mammary epithelial cells and epithelial melanocytes but not in a variety of breast carcinoma or melanoma cells and only at low levels in isolated human breast tumor tissue.² It inhibits 22(R)-hydroxy cholesterol-induced activation of LXRβ and LXRα in a reporter assay (IC50s = 76 and 362 nM, respectively) but is also a partial agonist of LXRs, increasing protein levels of Nur77, NOR-1, LC3-I, and LC3-II in B16/F10 murine melanoma cells.⁴ It is selective for modulation of LXRα and LXRβ over the pregnane X receptor (PXR), aryl hydrocarbon receptor (AhR), vitamin D receptor (VDR), retinoid X receptor γ (RXRγ), retinoic acid receptor α (RARα), peroxisome proliferator-activated receptor α (PPARα), PPARγ, glucocorticoid receptor, androgen receptor, estrogen receptor α (ERα), and ERβ at 2.5 µM. It also increases protein levels of LC3-II in B16/F10 and SK-MEL-28 cancer cells when used at concentrations of 2.5 and 5 µM and induces autophagic cell death in the same cell types at 2.5 µM. DDA (0.37 µg/kg) reduces tumor growth in a B16/F10 murine model of melanoma and a TS/A murine mammary cancer model and induces cancer cell differentiation in vitro and in vivo.²