QR336

QR336 is an orally bioavailable small molecule Liver X Receptor (LXR) agonist originally developed by QuatRx Pharmaceuticals for the treatment of dyslipidemia and atherosclerosis. As a nuclear receptor agonist, QR336 targets both LXRα (NR1H3) and LXRβ (NR1H2), which serve as critical sensors of cholesterol levels. Upon activation, these receptors upregulate the expression of genes involved in reverse cholesterol transport, such as the ATP-binding cassette transporters ABCA1 and ABCG1, facilitating the efflux of cholesterol from peripheral tissues (including arterial macrophages) to high-density lipoprotein (HDL) particles. QR336 was specifically engineered to optimize the therapeutic window by promoting cholesterol clearance while attempting to mitigate the common LXR-agonist side effect of hepatic lipogenesis, which is typically driven by LXRα-mediated activation of SREBP-1c and fatty acid synthase. Despite showing promise in preclinical models for increasing HDL-C and reducing atherosclerotic lesions, the clinical development of QR336 was discontinued following early-stage human trials.