2. Metabolic Enzyme/Protease
  3. ATP Citrate Lyase
  4. ACLY-IN-4

ACLY-IN-4 is an ATP-citrate lyase (ACLY) inhibitor with an IC50 of 0.022 μM and a Kd of 0.19 μM. ACLY-IN-4 binds to the allosteric binding site of ACLY. ACLY-IN-4 exhibits hypolipidemic, anti-steatotic, insulin sensitivity-improving, anti-oxidative stress, anti-inflammatory and anti-fibrotic activities. ACLY-IN-4 alleviates hepatic steatosis, systemic insulin resistance, oxidative stress, hepatic inflammation and fibrosis. ACLY-IN-4 can be used for the research of metabolic dysfunction-associated steatohepatitis.

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ACLY-IN-4

ACLY-IN-4 Chemical Structure

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ACLY-IN-4 Related Antibodies

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Description

ACLY-IN-4 is an ATP-citrate lyase (ACLY) inhibitor with an IC50 of 0.022 μM and a Kd of 0.19 μM. ACLY-IN-4 binds to the allosteric binding site of ACLY. ACLY-IN-4 exhibits hypolipidemic, anti-steatotic, insulin sensitivity-improving, anti-oxidative stress, anti-inflammatory and anti-fibrotic activities. ACLY-IN-4 alleviates hepatic steatosis, systemic insulin resistance, oxidative stress, hepatic inflammation and fibrosis. ACLY-IN-4 can be used for the research of metabolic dysfunction-associated steatohepatitis[1].

In Vitro

ACLY-IN-4 (Compound C1) (50 μM; 4 h with 1 mM OA) inhibits Oleic acid (HY-N1446)-induced lipid accumulation in shNC HepG2 cells, but this effect is attenuated in shACLY HepG2 cells, indicating an ACLY-dependent mechanism[1].
ACLY-IN-4 (50 μM; 24 h with 1 mM OA) downregulates lipogenic gene expression (FASN, ACC1, SREBP-1c) in Oleic acid-induced shNC HepG2 cells via an ACLY-dependent mechanism[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ACLY-IN-4 Related Antibodies

Real Time qPCR[1]

Cell Line: oleic acid (OA)-induced shNC and shACLY HepG2 cells
Concentration: 50 μM
Incubation Time: 24 h (with 1 mM OA)
Result: Significantly downregulated mRNA expression of FASN, ACC1, and SREBP-1c in OA-induced shNC HepG2 cells.
Abolished the downregulatory effect on mRNA expression of FASN, ACC1, and SREBP-1c in OA-induced shACLY HepG2 cells.
Parmacokinetics
Species Dose Route Cmax T1/2 AUCINF_obs CL Bioavailability
Mice[1] 10 mg/kg i.p. 2062 ng/mL 0.42 h 1019 ng·h/mL 413 mL/min/kg 255 %
In Vivo

ACLY-IN-4 (Compound C1) (10-30 mg/kg; i.p.; daily; 8 weeks) significantly alleviates hepatic steatosis, systemic insulin resistance, oxidative stress, inflammation, and fibrosis in a HFD-induced murine MASH model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6J (male, 8 weeks old, 18-20 g, HFD-induced MASH)[1]
Dosage: 10 mg/kg; 30 mg/kg
Administration: i.p.; daily; 8 weeks
Result: Reduced average body weight to 46.0 g (10 mg/kg) and 32.9 g (vs 49.5 g in HFD control).
Significantly reduced serum triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), low-density lipoprotein cholesterol (LDL-C), liver weight, hepatic TG, and hepatic T-CHO at 10 mg/kg.
Restored serum high-density lipoprotein cholesterol (HDL-C) levels at 10 mg/kg.
Significantly reduced hepatic lipid accumulation (confirmed by Oil Red O staining) at 10 mg/kg.
Suppressed hepatic mRNA expression of lipogenic markers (FASN, LXR, SREBP-1c, HMGCR, ACC1, CD36) and pro-inflammatory/fibrotic markers (CD68, TNF-α, NLRP3, ASC, α-SMA) at 10 mg/kg.
Restored mRNA expression of fatty acid oxidation markers (PPARα, CPT1, PPARγ, AMPKα1) at 10 mg/kg.
Reduced hepatic malondialdehyde (MDA) levels at 10 mg/kg.
Reduced liver protein levels of FASN, ACC1, NLRP3, ASC, α-SMA while increasing PPARα levels at 10 mg/kg.
Showed greater reductions in body weight, serum and hepatic lipid parameters, liver weight, and hepatic lipid accumulation than the 10 mg/kg dose at 30 mg/kg.
Produced similar significant effects on gene and protein expression of lipogenic, fatty acid oxidation, inflammatory, and fibrotic markers as the 10 mg/kg dose at 30 mg/kg.
Nearly restored hepatocellular morphology to match the standard diet control group (confirmed by H&E staining) at 30 mg/kg.
Molecular Weight

286.24

Formula

C15H10O6
SMILES

O=C(C1=CC2=CC(O)=C(C=C2O1)O)C3=CC(O)=C(C=C3)O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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ACLY-IN-4 Related Classifications

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ACLY-IN-4ATP Citrate LyaseACLYATP-citrate lyaseSREBP-1cmetabolic dysfunction-associated fatty liver diseaseHepG2 cellsmetabolic dysfunction-associated steatohepatitisoleic acidFASNACC1lipogenic geneInhibitorinhibitorinhibit

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