AZ876

SKU: orb1302023

Description

AZ876 is a potent and selective liver X receptor (LXR) agonist, demonstrating high affinity for both human LXRα (Ki/EC50 = 7/6 nM) and LXRβ (Ki/EC50 = 11/73 nM). This small molecule is a valuable research tool for studying LXR-mediated pathways in atherosclerosis, lipid metabolism, and inflammation in both cellular and animal models.

Research Area

Metabolism Research

Key Properties

• CAS Number: 898800-26-5
• MW: 439.57
• Purity: 99.86%
• Formula: C₂₄H₂₉N₃O₃S
• SMILES: CC(C)(C)N1C(=O)C(Nc2ccc(cc2)N2CCCCC2)=C(c2ccccc2)S1(=O)=O
• Target: Liver X Receptor
• Solubility: DMSO:55 mg/mL (125.12 mM);5% DMSO+40% PEG300+5% Tween 80+50% Saline:2.5 mg/mL (5.69 mM)

Bioactivity

• Target IC50:
  LXR:6 nM (EC50, cell free)
• In Vivo:
  Low-dose AZ876 had no effect on plasma or liver lipids, whereas high-dose AZ876 increased plasma triglycerides and reduced cholesterol compared with controls. Low-dose AZ876 reduced lesion area; and high-dose AZ876 strongly decreased lesion area, lesion number, and severity. In either dose, AZ876 did not affect lesion composition . Cardiac hypertrophy was induced in C57Bl6/J mice via transverse aortic constriction (TAC) for 6 weeks. During this period, mice received chow supplemented or not with AZ876 (20 μmol/kg/day). In murine hearts, LXRα protein expression was up-regulated ～7-fold in response to TAC. LXR activation with AZ876 attenuated this increase, and significantly reduced TAC-induced increases in heart weight, myocardial fibrosis, and cardiac dysfunction without affecting blood pressure .
• In Vitro:
  AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes and further inhibited prohypertrophic and profibrotic TGFβ-Smad2/3 signaling. In cardiomyocytes, phenylephrine-stimulated cellular hypertrophy was significantly decreased in AZ876-treated cells. In cardiac fibroblasts, AZ876 prevented TGFβ- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, α-smooth muscle actin .
• Animal Research:
  Cardiac hypertrophy was induced in male C57Bl6/J mice via transverse aortic constriction (TAC) for 6 weeks. During this period, sham and TAC-operated mice were randomized to receive either regular chow (control) or chow supplemented with AZ876 (20 μmol/kg/day). Cardiac function was assessed with echocardiography and invasive haemodynamics. In vitro studies were performed in isolated neonatal rat ventricular myocytes (NRVMs) and adult rat cardiac fibroblasts. Leucine and proline tracer assays were used to measure protein and collagen synthesis, respectively .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AZ 876, AZ-876, AZ876, LXR, inhibit, Liver X Receptor, LiverXReceptor, Liver X receptor, Inhibitor

Compound Identifiers

PubChem CID

11655079