2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. ACSL Family

ACSL Family

Long-chain acyl-CoA synthetase (ACSL) serves as a central regulatory node in cellular lipid metabolism, responsible for activating free long-chain fatty acids into acyl-CoAs, thereby channeling these fatty acids into downstream pathways such as oxidative energy production or complex lipid synthesis. The mammalian ACSL family comprises five isoforms-ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6-which exhibit significant differences in their tissue distribution, subcellular localization, and substrate preferences[1].
Specifically, ACSL3 inhibits lipid peroxidation by enriching monounsaturated fatty acids, thereby protecting tumor cells from damage. ACSL4 is predominantly enriched in adrenal and brain tissues; it specifically favors the activation of 20-carbon polyunsaturated fatty acids (PUFAs), acts as a core executor driving ferroptosis, and participates in the JAK-STAT1-IRF1 signaling axis. In various malignancies-such as hepatocellular carcinoma and breast cancer-ACSL4 exerts pro-tumorigenic effects and is associated with poor prognosis. Conversely, ACSL5 is primarily distributed in the intestine, localizes to mitochondria, and prefers 16-18 carbon fatty acids; it suppresses the Wnt signaling pathway by mediating the palmitoylation of the Wnt2B protein, typically functioning as a tumor suppressor gene and exerting protective effects in pancreatic cancer. However, in gastric cancer, ACSL5 is aberrantly overexpressed due to promoter hypomethylation, which paradoxically promotes the proliferation and metastasis of tumor cells[1][2][3].
The expression of the ACSL family is under strict regulation by signaling pathways-such as JAK-STAT and PPAR-as well as epigenetic mechanisms; functional abnormalities within this family are closely implicated in various malignancies-including hepatocellular carcinoma and breast cancer-as well as metabolic disorders. Inhibitors specifically targeting ACSL4 and ACSL5-such as troglitazone and tolcapone-hold potential for clinical application in precisely disrupting tumor metabolism or mitigating tissue damage[1][2][3].

ACSL Family Isoform Specific Products:

ACSL Family Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-N6707
    Triacsin C
    		Inhibitor 99.08%
    Triacsin C (WS 1228A), is an orally active and intracellular long-chain acyl-CoA synthetases (ACSL) inhibitor, which can be isolated from Streptomyces aureofaciens. Triacsin C inhibits TAG accumulation into lipid droplets (LD) by suppressing ACSL activity. Triacsin C exhibits highly inhibitory effect against rotavirus replication.
    Triacsin C
  • HY-173432
    LIBX-A401
    		Inhibitor 99.9%
    LIBX-A401 is a selective long-chain acyl-CoA synthetase 4 (ACSL4) inhibitor with a human IC50 values of 0.38 μM and a Kd of 0.72 μM. LIBX-A401 binds to ACSL4 in an ATP-dependent manner, stabilizes the C-terminal domain, alters the fatty acid gate region, and interacts with residues A329 and Q302 within the fatty acid binding site. LIBX-A401 exhibits anti-ferroptosis properties in cells. LIBX-A401 can be used for the researches of cancer and parkinson's disease.
    LIBX-A401
  • HY-177705
    ACSL5-IN-2
    		Inhibitor 99.51%
    ACSL5-IN-2 (Compound B) is an Acyl CoA synthetase 5 (ACSL5) inhibitor. ACSL5-IN-2 can block the conversion of long-chain fatty acids (such as palmitic acid and oleic acid) into acyl-CoA, and intervene in the fatty acid metabolism pathway. ACSL5-IN-2 can inhibit cancer cells growth. ACSL5-IN-2 can be used for the research of cancer and metabolic disease, such as colon cancer and dysfunction-associated Steatohepatitis.
    ACSL5-IN-2
  • HY-175328
    LIBX-A403
    		Inhibitor 98.28%
    LIBX-A403 is a potent, selective and reversible ACSL4 inhibitor with a human IC50 of 0.049 μM and a Kd of 0.29 μM. LIBX-A403 binds in the ACSL4 fatty acid pocket in an ATP-dependent manner. LIBX-A403 prevents cell ferroptosis. LIBX-A403 can be used for the researches of cancer and parkinson's disease.
    LIBX-A403
  • HY-177704
    ACSL5-IN-1
    		Inhibitor 99.88%
    ACSL5-IN-1 (Compound A) is an ACSL5 inhibitor with body weight-reducing activity. ACSL5-IN-1 inhibits ACSL5, an enzyme linked to fatty acid metabolism. ACSL5-IN-1 reduces body weight in diet-induced obesity mice. ACSL5-IN-1 can be used for the research of obesity, metabolic dysfunction-associated steatohepatitis, metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, acute myeloid leukemia, colorectal cancer, and breast cancer.
    ACSL5-IN-1
  • HY-177850
    ACSL5-IN-3
    		99.74%
    ACSL5-IN-3 (page 115 line 11) is an ACSL5 inhibitor. ACSL5-IN-3 can be used for research of tumours, digestive system diseases, and endocrine and metabolic diseases.
    ACSL5-IN-3
  • HY-186096
    LP-856866
    		Inhibitor 99.92%
    LP-856866 is an orally active ACSL5 inhibitor, with IC50 values of 8 nM and 4 nM against mouse and human ACSL5, respectively, and IC50 values of 6 nM and 17 nM against mouse and human ACSL1, respectively. LP-856866 induces delayed gastric emptying, promotes GLP-1 release, reduces food intake, decreases body weight and body fat mass, preserves lean body mass, improves glucose homeostasis, enhances insulin sensitivity, reduces hepatic lipid accumulation, and lowers serum triglyceride and total cholesterol levels. LP-856866 is applicable to research on diet-induced obesity.
    LP-856866
  • HY-186095
    LP-911888
    		Inhibitor 99.83%
    LP-911888 is an orally active ACSL5/ACSL1 inhibitor, with IC50 values of 1 nM and 3 nM against mouse and human ACSL5, and IC50 values of 2 nM and 9 nM against mouse and human ACSL1, respectively. LP-911888 inhibits intestinal triglyceride uptake; it also reduces body weight and food consumption in diet-induced obese mice, and delays gastric emptying by activating the ileal brake pathway. LP-911888 can be used in studies of diet-induced obesity.
    LP-911888
  • HY-121246
    Fluorofenidone
    		Inhibitor 99.78%
    Fluorofenidone (AKF-PD) is an orally active compound with anti-fibrotic, antioxidant, and anti-inflammatory pharmacological effects. Fluorofenidone downregulates the expression of ACSL4, upregulates GPX4 expression and inhibits the NF-κB signaling pathway to alleviate inflammation and fibrosis. Fluorofenidone ameliorates cholestasis and fibrosis by inhibiting hepatic Erk/-Egr-1 signaling and Tgfβ1/Smad pathway in mice. Fluorofenidone demonstrates protective effects against chronic lung injury in mice. Fluorofenidone can be used for the study of chronic obstructive pulmonary disease (COPD), pulmonary interstitial fibrosis (PIF) and non-small cell lung cancer (NSCLC).
    Fluorofenidone
  • HY-RS00202
    ACSL4 Human Pre-designed siRNA Set A
    		Inhibitor

    ACSL4 Human Pre-designed siRNA Set A contains three designed siRNAs for ACSL4 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    ACSL4 Human Pre-designed siRNA Set A
  • HY-175327
    LIBX-A402
    		Inhibitor 98.71%
    LIBX-A402 is a selective, ATP-dependent inhibitor of ACSL4 (hACSL4, IC50=0.33 μM, Kd=3.3 μM) and an inhibitor of ferroptosis. LIBX-A402 targets the fatty acid-binding pocket of ACSL4 and prevents cells from undergoing ferroptosis. LIBX-A402 can be used in the research of cancer and Parkinson's disease.
    LIBX-A402
  • HY-RS16556
    Acsl4 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Acsl4 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Acsl4 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Acsl4 Mouse Pre-designed siRNA Set A
  • HY-RS16244
    Acsl4 Rat Pre-designed siRNA Set A
    		Inhibitor

    Acsl4 Rat Pre-designed siRNA Set A contains three designed siRNAs for Acsl4 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Acsl4 Rat Pre-designed siRNA Set A
  • HY-113167
    2-Phosphoglyceric acid
    		Inhibitor
    2-Phosphoglyceric acid (DL-2-phosphoglyceric acid) is a glycolytic substrate that is catalyzed by enolase to form phosphoenolpyruvate ester (PEP). 2-Phosphoglyceric acid inhibits the ferroptosis pathway by down-regulating ACSL4 and up-regulating GPX4, and has significant neuroprotective effects. 2-Phosphoglyceric acid reflects the overall metabolic state and flux of the cell.
    2-Phosphoglyceric acid
  • HY-RS00200
    ACSL1 Human Pre-designed siRNA Set A
    		Inhibitor

    ACSL1 Human Pre-designed siRNA Set A contains three designed siRNAs for ACSL1 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    ACSL1 Human Pre-designed siRNA Set A
  • HY-RS16256
    Acsl5 Mouse Pre-designed siRNA Set A
    		Inhibitor
    Acsl5 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Acsl5 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Acsl5 Mouse Pre-designed siRNA Set A
  • HY-RS00201
    ACSL3 Human Pre-designed siRNA Set A
    		Inhibitor

    ACSL3 Human Pre-designed siRNA Set A contains three designed siRNAs for ACSL3 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    ACSL3 Human Pre-designed siRNA Set A
  • HY-RS16255
    Acsl1 Mouse Pre-designed siRNA Set A
    		Inhibitor
    Acsl1 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Acsl1 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Acsl1 Mouse Pre-designed siRNA Set A
  • HY-RS20850
    Acsl6 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Acsl6 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Acsl6 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Acsl6 Mouse Pre-designed siRNA Set A
  • HY-175698
    Ferroptosis inducer-9
    		Activator
    Ferroptosis inducer-9 is a ferroptosis inducer and colchicine site tubulin polymerization inhibitor. Ferroptosis inducer-9 inhibits MCF-7 cell growth with an IC50 of 14 nM and inhibits [3H]colchicine binding. Ferroptosis inducer-9 reduces expression of GPX4 and FTH, increases COX2 and ACSL4, lowers GSH, NADP+, and NADPH levels, increases LPO, MDA, and Fe(II) levels, and decreases SOD concentrations. Ferroptosis inducer-9 demonstrates significant anti-tumor efficacy in HCT116 CRC xenograft model. Ferroptosis inducer-9 can be used for the study of triple negative breast cancer (TNBC) and colorectal cancer (CRC).
    Ferroptosis inducer-9
ACSL Family Isoform Comparison

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