Dendrogenin A

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. It is formed from 5,6alpha-epoxy cholesterol via conjugation with histamine by DDA synthase. 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. It inhibits 22(R)-hydroxy cholesterol-induced activation of LXRbeta and LXRalpha 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. It is selective for modulation of LXRalpha and LXRbeta over the pregnane X receptor (PXR), aryl hydrocarbon receptor (AhR), vitamin D receptor (VDR), retinoid X receptor gamma (RXRgamma), retinoic acid receptor alpha (RARalpha), peroxisome proliferator-activated receptor alpha (PPARalpha), PPARgamma, glucocorticoid receptor, androgen receptor, estrogen receptor alpha (ERalpha), and ERbeta 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.Formal Name: (3beta,5alpha,6beta)-6-[[2-(1H-imidazol-5-yl)ethyl]amino]-cholestane-3,5-diol. CAS Number: 1191043-85-2. Synonyms: DDA. Molecular Formula: C32H55N3O2. Formula Weight: 513.8. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml. SMILES: C[C@@]([C@@]1(C2)O)(CC[C@@H]2O)[C@](CC3)([H])[C@](C[C@H]1NCCC4=CN=CN4)([H])[C@@](CC[C@]5([H])[C@H](C)CCCC(C)C)([H])[C@]35C. InChi Code: InChI=1S/C32H55N3O2/c1-21(2)7-6-8-22(3)26-9-10-27-25-17-29(34-16-13-23-19-33-20-35-23)32(37)18-24(36)11-15-31(32,5)28(25)12-14-30(26,27)4/h19-22,24-29,34,36-37H,6-18H2,1-5H3,(H,33,35)/t22-,24+,25+,26-,27+,28+,29-,30-,31-,32+/m1/s1. InChi Key: AVFNYTPENXWWCA-BULFVYHESA-N.