SC 26196 is an orally active Delta6 desaturase (D6D, FADS2) inhibitor that regulates lipid metabolism by inhibiting the conversion of linoleic acid and α-linolenic acid into long-chain unsaturated fatty acids[1-2]. SC 26196 is applicable for research related to inflammatory diseases and lipid metabolism disorders[3-4].
In vitro, in skin fibroblasts, coronary artery smooth muscle cells, and astrocytes, SC 26196 (2μM; 24 hours) inhibited the desaturation of 2μM [1-14C]18:2n-6 and significantly reduced the synthesis of arachidonic acid, EPA, and DHA[5]. During the differentiation of 3T3-L1 adipocytes, SC 26196 (5μM; 8 days) blocked the conversion of α-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPAn-3), and reduced triacylglycerol accumulation in adipocytes. SC 26196 treatment increased the release of non-esterified fatty acids and glycerol into the culture medium and decreased the expression of the fatty acid re-esterification markers PEPCK and CD36[6].
In vivo, in athymic mice bearing U-87 MG cell xenografts, SC 26196 (30mg/kg) administered via intraperitoneal injection (every three days for four weeks). SC 26196 synergistically inhibited the growth of U-87 MG xenograft tumors when combined with radiation therapy (5Gy local X-ray irradiation, every three days)[7]. In ApcMin/+ mice bearing HT-29 colon cancer cell xenografts, dietary administration of SC 26196 (100mg/kg) for seven weeks. SC 26196 reduced number of intestinal tumors and a significant decrease in tumor size[8].
References:
[1] Sibbons CM, Irvine NA, Pérez-Mojica JE, et al. Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells. Front Immunol. 2018 Mar 5;9:432.
[2] Hargrave-Barnes KM, Azain MJ, Miner JL. Conjugated linoleic acid-induced fat loss dependence on Delta6-desaturase or cyclooxygenase. Obesity (Silver Spring). 2008 Oct;16(10):2245-52.
[3] Duffin KL, Obukowicz MG, Salsgiver WJ, et al. Lipid remodeling in mouse liver and plasma resulting from delta6 fatty acid desaturase inhibition. Lipids. 2001 Nov;36(11):1203-8.
[4] Obukowicz MG, Welsch DJ, Salsgiver WJ, et al. Novel, selective delta6 or delta5 fatty acid desaturase inhibitors as antiinflammatory agents in mice. J Pharmacol Exp Ther. 1998 Oct;287(1):157-66.
[5] Harmon SD, Kaduce TL, Manuel TD, et al. Effect of the delta6-desaturase inhibitor SC-26196 on PUFA metabolism in human cells. Lipids. 2003 Apr;38(4):469-76.
[6] Wang C, MacIntyre B, Mutch DM. Inhibition of Δ-6 desaturase reduces fatty acid re-esterification in 3T3-L1 adipocytes independent of changes in n3-PUFA cellular content. Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jul;1867(7):159160.
[7] Wang J, Liang H, Sun M, et al. Delta-6-desaturase inhibitor enhances radiation therapy in glioblastoma in vitro and in vivo. Cancer Manag Res. 2018 Dec 7;10:6779-6790.
[8] Hansen-Petrik MB, McEntee MF, Johnson BT, et al. Selective inhibition of Delta-6 desaturase impedes intestinal tumorigenesis. Cancer Lett. 2002 Jan 25;175(2):157-63.
SC 26196是一种具有口服活性的Delta6去饱和酶（D6D, FADS2）抑制剂，SC 26196可抑制亚油酸和α-亚麻酸向长链不饱和脂肪酸的转化以调控脂质代谢[1-2]。SC 26196可用于炎症相关疾病、脂代谢紊乱的相关研究[3-4]。
在体外，在皮肤成纤维细胞、冠状动脉平滑肌细胞和星形胶质细胞中，SC 26196（2μM；24h）可抑制2μM [1-14C]18:2n-6的去饱和作用，并显著降低花生四烯酸、EPA和DHA的合成[5]。在3T3-L1脂肪细胞分化过程中，SC 26196（5μM；8天）可阻断α-亚麻酸（ALA）向二十碳五烯酸（EPA）和二十二碳五烯酸（DPAn-3）的转化，并减少脂肪细胞中甘油三酯的积累，SC 26196处理增加了培养基中非酯化脂肪酸和甘油的释放，降低了脂肪酸再酯化的标志物PEPCK和CD36的表达[6]。
在体内，SC 26196(30mg/kg)通过腹膜内注射（每三天一次，持续四周）处理携带有U-87 MG细胞异种移植瘤的无胸腺小鼠，SC 26196联合放射治疗（5Gy局部X射线照射，每三天一次）可协同抑制U-87 MG异种移植瘤的生长[7]。SC 26196(100mg/kg)通过饮食处理HT-2结肠癌细胞异种移植的ApcMin/+小鼠（处理七周），SC 26196导致肠道肿瘤数量减少，肿瘤尺寸显著减小[8]。