LXR-623

LXR-623 is a synthetic, orally bioavailable small molecule that acts as a highly selective and brain-penetrant agonist of liver X receptors (LXR) alpha and beta. It functions as a partial agonist at LXRα and a full agonist at LXRβ, with IC50 values of 179 nM for LXRα and 24 nM for LXRβ[1][4][7]. The drug was initially developed by Pfizer. Mechanistically, activation of LXRs by LXR-623 upregulates cholesterol transporters such as ABCA1 and ABCG1, enhancing reverse cholesterol transport—a process believed to shuttle cholesterol from peripheral tissues back to the liver—and suppresses LDL receptor (LDLR) expression[5][6][7]. In preclinical models, this leads to reduced cellular cholesterol content. LXR-623 has demonstrated activity in animal models of atherosclerosis by promoting reverse cholesterol transport and reducing plaque formation[5][7]. It also shows potential anti-tumor effects in glioblastoma multiforme (GBM) models by inducing tumor cell death through depletion of intracellular cholesterol[6]. Additionally, it has been shown to inhibit flavivirus replication in vitro via upregulation of antiviral cytokines and disruption of viral vesicle biogenesis[2]. Despite promising preclinical results—including CNS penetration—development was discontinued after Phase 1 clinical trials due to central nervous system-related adverse events observed at higher doses in healthy participants[3][5].

Other names

LX-623LX623LX 623