LXR-623

LXR-623 (CAS 875787-07-8) is an orally bioavailable liver X receptor modulator acting as a partial LXRα and full LXRβ agonist, also known as WAY-252623 and PF-05402814. The compound is brain-penetrant and demonstrates activity across cardiovascular, oncological, and neurodegenerative disease models. Enamine offers LXR 623 as a high-purity screening sample for in vitro and in vivo research applications.

LXR-623 molecular formula is C₂₁H₁₂ClF₅N₂ with a molecular weight of 422.78 g/mol. The LXR-623 structure is based on a 2H-indazole scaffold with a trifluoromethyl group at position 7, a 4-fluorophenyl substituent at C-3, and a 2-chloro-4-fluorobenzyl group at N-2. LXR-623 chemical name is 2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole; the LXR-623 WAY-252623 SMILES is FC(C=C1)=CC=C1C2=C3C(C(F)(F)F)=CC=C3N=N2CC4=CC=C(F)C=C4Cl, and the LXR-623 structure SMILES string is widely referenced in computational screening workflows. The compound is registered under LXR-623 CAS 875787-07-8.

Application of LXR-623

LXR 623 is applied in research targeting cholesterol homeostasis, reverse cholesterol transport, and LXR-driven gene regulation. Its dual LXRα/β activity makes it relevant for studies on atherosclerosis, glioblastoma, Alzheimer's disease, and inflammatory pathway modulation. WAY-252623 is used as a reference agonist in nuclear receptor screening and target validation workflows requiring CNS-penetrant compounds.

In Vitro

LXR-623 inhibits LXRα and LXRβ with IC₅₀ values of 179 nM and 24 nM, respectively. In cell-based assays, the compound upregulates ABCA1 and ABCG1 expression in human PBMCs, monocytes, and T- and B-cells. LXR-623 selectively kills glioblastoma multiforme (GBM) cells in an LXRβ- and cholesterol-dependent manner, while showing limited toxicity toward normal cells. It also modulates AKT/MDM2/p53 signaling in triple-negative breast cancer cell lines.

In Vivo

In the murine LDLR⁻/⁻ atherosclerosis model, LXR 623 reduces lesion progression without increasing hepatic lipogenesis. In nonhuman primates, oral dosing with WAY-252623 reduced total cholesterol by 50–55% and LDL-cholesterol by 70–77% in a dose-dependent manner. In GBM mouse models, the compound causes tumor regression and prolongs survival. A Phase 1 clinical study confirmed dose-dependent induction of ABCA1 and ABCG1 in peripheral blood following single oral doses in healthy participants.

Biochemical and Physiological Actions

LXR-623 binds the ligand-binding domain of liver X receptors and promotes transcription of genes involved in cholesterol efflux, including ABCA1, ABCG1, ABCG5, and ABCG8. As a partial LXRα agonist, it activates cholesterol transport pathways with reduced hepatic lipogenic side effects compared to full LXRα agonists. Through LXRβ activation in the CNS, PF-05402814 reduces amyloid-β levels and modulates neuroinflammatory signaling, supporting its investigation in Alzheimer's disease models.

Features and Benefits of LXR-623

LXR-623 (WAY-252623, CAS 875787-07-8) provides a well-characterized pharmacological profile for diverse research areas:

• potent LXRβ agonism (IC₅₀ 24 nM) with partial LXRα activity, enabling receptor-subtype-specific studies
• blood-brain barrier penetration supporting CNS-focused research
• validated activity in cardiovascular, oncological, and neurodegenerative models
• oral bioavailability with clinical Phase 1 data available

When sourced as EBC-501088, the compound is provided with analytical quality control data for reliable integration into screening and mechanistic studies.