CAY10566 is a selective stearoyl-CoA desaturase 1 (SCD1) inhibitor (mouse: IC₅₀= 4.5nM; human: IC₅₀=4.5nM). CAY10566 blocks the conversion of saturated long-chain fatty acyl-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs (IC₅₀=7.9nM or 6.8nM). CAY10566 can be used in studies related to fatty acid metabolism regulation, metabolic diseases, as well as colorectal cancer, liver cancer, and ovarian cancer[1-4].
In vitro, Swiss 3T3 cells were treated with CAY10566 (0.1nM–10μM) for 48 hours. CAY10566 inhibited cell proliferation in a concentration-dependent manner[5]. Mia-PaCa2 or CFPAC-1 human pancreatic cancer cells were treated with CAY10566 (10μM) for 48 hours. CAY10566 reduced the expression of ACLY, FASN, ACACA, and ACACB genes in the cells[6].
In vivo, after establishing ischemic stroke (MCAO/R) model in mice, CAY10566 (20mg/kg; once daily) was administered by oral gavage to MCAO/R mice for 3 days starting 2 hours after reperfusion. CAY10566 significantly reduced cerebral infarct volume, alleviated neuronal apoptosis, and improved cognitive and motor functions of mice[7]. CAY10566 (7.5mg/kg; once every three days) was intraperitoneally injected into C57BL/6 mice fed a high-fat diet for 14 weeks. CAY10566 significantly ameliorated hepatic steatosis, reduced hepatic lipid droplet accumulation, and enhanced AMPK-mediated lipophagy in the mice[8].
References:
[1] Masuda M, Ting TC, Levi M, et al. Activating transcription factor 4 regulates stearate-induced vascular calcification. J Lipid Res. 2012 Aug;53(8):1543-52.
[2] Liu G, Lynch JK, Freeman J, et al. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors. J Med Chem. 2007 Jun 28;50(13):3086-100.
[3] de Lima Luna AC, Forti FL. Modulation of SCD1 activity in hepatocyte cell lines: evaluation of genomic stability and proliferation. Mol Cell Biochem. 2021 Sep;476(9):3393-3405.
[4] Kamphorst JJ, Cross JR, Fan J, et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A. 2013 May 28;110(22):8882-7.
[5] Koeberle A, Shindou H, Harayama T, et al. Palmitoleate is a mitogen, formed upon stimulation with growth factors, and converted to palmitoleoyl-phosphatidylinositol. J Biol Chem. 2012 Aug 3;287(32):27244-54.
[6] Zhang X, Zhu B, Yan J, et al. Matrix stiffness boosts PDAC chemoresistance via SCD1-dependent lipid metabolic reprogramming. Regen Biomater. 2025 Jun 16;12:rbaf056.
[7] Li S, Li X Jr, Peng L, et al. Inhibition of SCD1 attenuates neuroinflammation and brain injury after cerebral ischemia-reperfusion. Brain Res Bull. 2026 Feb;235:111693.
[8] Zhou Y, Zhong L, Yu S, et al. Inhibition of stearoyl-coenzyme A desaturase 1 ameliorates hepatic steatosis by inducing AMPK-mediated lipophagy. Aging (Albany NY). 2020 Apr 23;12(8):7350-7362.
CAY10566是一种选择性硬脂酰辅酶A去饱和酶1（SCD1）抑制剂（小鼠：IC50=4.5nM；人：IC50=4.5nM）。CAY10566可阻断饱和长链脂肪酸辅酶A（LCFA-CoAs）向单不饱和LCFA-CoAs的转化（IC50=7.9nM或6.8nM）。CAY10566可用于脂肪酸代谢调节、代谢性疾病以及结直肠癌、肝癌和卵巢癌等相关研究[1-4]。
在体外，CAY10566（0.1nM–10μM）处理Swiss 3T3细胞48小时。CAY10566以浓度依赖性地抑制细胞增殖[5]。CAY10566（10μM）处理Mia-PaCa2或CFPAC-1人胰腺癌细胞48小时。CAY10566可降低细胞中ACLY、FASN、ACACA、ACACB基因的表达[6]。
在体内，在小鼠建立缺血性卒中模型（MCAO/R）2小时后，CAY10566（20mg/kg；每天一次）灌胃于MCAO/R小鼠3天。CAY10566显著减少了脑梗死体积、减轻了神经元凋亡，并改善了小鼠的认知和运动功能[7]。CAY10566（7.5mg/kg；每三天一次）腹腔注射于高脂饮食的C57BL/6小鼠，14周。CAY10566显著改善了小鼠的肝脏脂肪变性，减少了肝脏脂滴积累，并增强了AMPK介导的脂噬[8]。