|Molecular Weight||424.3 g/mol|
|Solubility||Soluble in DMSO at 25 mg/mL or ethanol at 20 mg/mL.|
The small-molecule BMS-303141 is a potent (IC50 = 0.13 μM) inhibitor of ATP-citrate lyase (ACL). ACL catalyzes the formation of cytosolic acetyl-CoA and oxaloacetate (OAA) in the cytosol, which is the key step for fatty acid and cholesterol biosynthesis. BMS-303141 also weakly inhibits acetyl-CoA carboxylase (ACC) isoforms ACC1 and ACC2. Treatment of high-fat fed mice with BMS-303141 reduced weight gain and decreased levels of plasma cholesterol, triglycerides, and glucose (1). BMS-303141 treatment of prostate cancer cells impaired cell proliferation or induced death in androgen-depleted, castration-resistant prostate cancer cells (2). Hepatocellular carcinoma cells responded to treatment with BMS-303141, reducing cell proliferation and promoting apoptosis. BMS-303141 is thought to induce endoplasmic reticulum (ER) stress and activate the p-eIF2α/ATF4/CHOP pathway to promote apoptosis. The combined treatment of a mouse xenograft model with BMS-303141 and a protein kinase inhibitor reduced tumor volume and weight (3).
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