The liver X receptors (LXRs) are nuclear receptors that act as ligand-dependent transcription factors. They modulate lipid, cholesterol, and carbohydrate metabolism and homeostasis. SR9243 is a cell-permeable LXR inverse agonist that induces LXR-corepressor interaction at nanomolar concentrations. It reduces cancer cell viability (IC50 values range from 15 to 104 nM) without cytotoxicity against non-malignant cells. SR9243 disrupts the Warburg effect in cancer cells, suppressing the expression of glycolytic and lipogenic genes and reducing glycolytic metabolites and lipid production. It is effective in vivo, blocking glycolytic and lipogenic gene expression and inducing apoptosis in colon cancer xenografts without inducing weight loss in mice.
SR9243 is used in new compounds targeting warburg effcts, killing cancer cells and inhibiting lipid production.
ChEBI: SR9243 is a sulfonamide resulting from the formal condensation of the sulfonic acid group of mesitylene-2-sulphonic acid with the amino group of 2-(m-bromophenyl)ethylamine in which the nitrogen is substituted by a 4-[m-(methylsulfonyl)phenyl]benzyl group. It has a role as an antineoplastic agent, an apoptosis inducer and a liver X receptor inverse agonist. It is a sulfonamide, a sulfone and a member of bromobenzenes.
SR9243 is able to profoundly inhibit tumor glycolysis, lipogenesis, and induce apoptotic cancer cell death without promoting weight loss in vivo. SR9243 inhibits tumor growth without profoundly repressing glycolytic gene expression, and inhibits tumor growth and lipogenesis without hepatotoxicity or inflammation in vivo[1].
[1] COLIN A FLAVENY. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis.[J]. Cancer Cell, 2015, 28 1: 42-56. DOI:
10.1016/j.ccell.2015.05.007
