A939572 is an orally effective and specific stearoyl-CoA desaturase 1 (SCD1) inhibitor with a reported IC₅₀ value of 6.3nM [1]. A939572 selectively inhibits SCD1, thereby reducing the synthesis of monounsaturated fatty acids such as oleic acid, and is commonly used in the study of metabolic diseases (e.g., non-alcoholic fatty liver disease, obesity) and cancers dependent on lipid metabolism (e.g., hepatocellular carcinoma, prostate cancer) [2] [3]. A939572, as a key lipid metabolism enzyme expressed in human pluripotent stem cells (hPSCs), has been used to induce hPSC cell death and to inhibit the proliferation of human non-small cell lung cancer (NSCLC) H1299 cells in vitro [4].
In UMUC3 cell，A939572 was used at concentrations of 3.2 or 25.6µg/mL to inhibit UMUC3 activity, and it significantly inhibited cell growth and colony formation[5]. In MCF-7 cells, the combination of low glucose and A939572 (10nM; 24h)-induced SCD1 inhibition significantly impairs the metabolic plasticity of cancer cells [6].
In a xenograft tumor model, A939572 treatment (30mg/kg; po; 35 days) significantly reduced tumor growth rate and weight in mice, inhibited lipid synthesis, and reduced chemotherapy resistance [7]. In an A498 ccRCC (clear cell renal cell carcinoma) xenograft model, A939572 treatment (30mg/kg; po; bid; 27 days) inhibited tumor cell growth, reduced tumor cell proliferation, and decreased the percentage of Ki67-positive cells in the cell nucleus [8].
References:
[1]. Roongta U V, Pabalan J G, Wang X, et al. Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy[J]. Molecular Cancer Research, 2011, 9(11): 1551-1561.
[2]. Kirad S, Puri S, Deepa P R, et al. An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors[J]. RSC advances, 2024, 14(41): 30487-30517.
[3]. Deutsch N, Dogiparthi J, Priefer R. Implications of Agonizing and Antagonizing Stearoyl-CoA Desaturase-1[J]. Medical Research Archives, 2020, 8(12).
[4]. Ben-David U, Gan Q F, Golan-Lev T, et al. Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen[J]. Cell stem cell, 2013, 12(2): 167-179.
[5]. Piao C, Cui X, Zhan B, et al. Inhibition of stearoyl CoA desaturase‐1 activity suppresses tumour progression and improves prognosis in human bladder cancer[J]. Journal of cellular and molecular medicine, 2019, 23(3): 2064-2076.
[6]. Zhu W, Lusk J A, Pascua V, et al. Combination of low glucose and SCD1 inhibition impairs cancer metabolic plasticity and growth in MCF-7 cancer cells: a comprehensive metabolomic and lipidomic analysis[J]. Metabolomics, 2024, 20(5): 112.
[7]. Deng J, Qin J H, Li X, et al. Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens[J]. Human Cell, 2024, 38(1): 13.
[8]. Von Roemeling C A, Marlow L A, Wei J J, et al. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma[J]. Clinical Cancer Research, 2013, 19(9): 2368-2380.
A939572是一种具有口服活性且特异性的硬脂酰辅酶A去饱和酶1（SCD1）抑制剂，其IC₅₀值为6.3nM[1]。A939572通过选择性抑制SCD1来降低油酸等单不饱和脂肪酸的合成，常用于代谢性疾病（如非酒精性脂肪性肝病、肥胖）及脂代谢依赖性癌症（如肝细胞癌、前列腺癌）的相关研究[2] [3]。A939572作为在人诱导多能干细胞（hPSCs）中表达的关键脂代谢酶，A939572已被用于诱导hPSCs死亡及在体外抑制人非小细胞肺癌（NSCLC）H1299细胞的增殖[4]。
在UMUC3细胞中，使用浓度为3.2或25.6µg/mL的A939572可抑制细胞活性，并显著抑制其生长与集落形成[5]。在MCF-7细胞中，低糖环境与A939572（10nM；24h）诱导的SCD1抑制共同作用，显著削弱了癌细胞的代谢可塑性[6]。
在异种移植肿瘤模型中，A939572治疗（30mg/kg；po；35d）显著降低了小鼠肿瘤的生长速度与重量，抑制了脂质合成并减少了化疗耐药性[7]。在A498 ccRCC（透明细胞肾细胞癌）异种移植模型中，A939572治疗（30mg/kg；po；bid；27d）能够抑制小鼠体内肿瘤细胞生长、减少肿瘤细胞增殖，并降低细胞核Ki67染色阳性细胞的百分比[8]。