Ly93是一种选择性鞘磷脂合成酶2（SMS2；IC50=91nM）抑制剂。
Cas No.:1883528-69-5
Sample solution is provided at 25 µL, 10mM.
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Ly93 is a selective sphingomyelin synthase 2 (SMS2) inhibitor with an IC50 of 91nM[1]. By inhibiting SMS2, Ly93 reduces sphingomyelin levels, thereby exerting anti-inflammatory and anti-atherosclerotic effects. Ly93 can be used in research related to atherosclerosis, dry eye disease, and epilepsy[2-3].
In vitro, Jurkat, Hut-102, and other T-cell malignancy cell lines were pretreated with Ly93 (10µM) for 1 hour, followed by treatment with compound V8 (4–6µM) for 6 hours. Ly93 attenuated V8-induced lysosomal membrane damage (reduction in Galectin-3-positive puncta) and decreased intracellular sphingomyelin levels[4]. NRK (normal rat kidney) cells were pretreated with Ly93 (35µM) for 30 minutes, followed by exposure to TcdB3 (0.2pM) for 4 hours. Ly93 blocked TcdB3-induced migrasome formation[5].
In vivo, high-fat diet-induced insulin-resistant C57BL/6 mice were treated with Ly93 (20-40mg/kg) via intragastric administration once daily for 12 weeks. Ly93 significantly improved insulin sensitivity[6]. In C57BL/6J mice, administration of Ly93 (100mg/kg) via gavage once daily for 7 days significantly reduced plasma sphingomyelin levels. Furthermore, apolipoprotein E knockout (apoE KO) mice on a Western diet were treated with Ly93 (12.5-40mg/kg) via gavage once daily for 7 weeks. Ly93 dose-dependently attenuated atherosclerotic lesions in both the aortic root and the entire aorta and reduced macrophage content within the lesions[7].
References:
[1] Hua F, Wang HR, Bai YF, et al. Substance P promotes epidural fibrosis via induction of type 2 macrophages. Neural Regen Res. 2023 Oct;18(10):2252-2259.
[2] Wan J, Hu Z, Zhu H, et al. The essential role of sphingolipids in TRPC5 ion channel localization and functionality within lipid rafts. Pharmacol Res. 2025 Mar;213:107648. doi: 10.1016/j.phrs.2025.107648. Epub 2025 Feb 7.
[3] Chen Q, Wei Y, Wang L, et al. Ly93 Inhibits Sphingomyelin Synthesis and Attenuates Inflammation and Injury in Dry Eye Conjunctival Organoids. Invest Ophthalmol Vis Sci. 2026 Feb 2;67(2):58.
[4] Qing Y, Guo Y, Zhao Q, et al. Targeting lysosomal HSP70 induces acid sphingomyelinase-mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies. Clin Transl Med. 2023 Mar;13(3):e1229.
[5] Li D, Yang Q, Luo J, et al. Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation. Cell Discov. 2024 Nov 5;10(1):112.
[6] Huang Y, Huang T, Zhen X, et al. A selective sphingomyelin synthase 2 inhibitor ameliorates diet induced insulin resistance via the IRS-1/Akt/GSK-3β signaling pathway. Pharmazie. 2019 Sep 1;74(9):553-558.
[7] Li Y, Huang T, Lou B, et al. Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor. Eur J Med Chem. 2019 Feb 1;163:864-882.
Ly93是一种选择性鞘磷脂合成酶2（SMS2；IC50=91nM）抑制剂[1]。Ly93通过抑制SMS2降低鞘磷脂水平，从而发挥抗炎、抗动脉粥样硬化等作用。Ly93可用于动脉粥样硬化、干眼症和癫痫的相关研究[2-3]。
在体外，Ly93（10µM）预处理Jurkat、Hut-102等T细胞恶性肿瘤细胞系1小时，随后以化合物V8（4–6µM）处理6小时。Ly93能够减弱V8诱导的溶酶体膜损伤，降低细胞内的鞘磷脂水平[4]。Ly93（35µM）预处理NRK（正常大鼠肾脏）细胞30分钟，随后以TcdB3（0.2pM）处理4小时，Ly93阻断了TcdB3诱导的迁移体形成[5]。
在体内，Ly93（20-40mg/kg）通过灌胃每天一次处理高脂饮食诱导的胰岛素抵抗C57BL/6小鼠，持续12周，显著改善了胰岛素敏感性[6]。Ly93（100mg/kg）通过灌胃每天一次处理C57BL/6J小鼠，持续7天，显著降低了血浆鞘磷脂水平。同时，Ly93（12.5-40mg/kg）通过灌胃每天一次处理apoE KO小鼠，持续7周。Ly93以剂量依赖性地减轻了主动脉根部和整个主动脉的动脉粥样硬化病变，并减少了病变中的巨噬细胞含量[7]。
| Cell experiment [1]: | |
Cell lines | NRK cells (normal rat kidney epithelial cell line) |
Preparation Method | NRK cells stably overexpressing Tspan4-mCherry were cultured on glass-bottom plates precoated with fibronectin for 10-12 hours. The cells were then pretreated with Ly93 (35µM) for 30 minutes, followed by exposure to TcdB3 (0.2pM) for 4 hours. |
Reaction Conditions | 35µM; pretreatment for 30min. |
Applications | Ly93 blocked TcdB3-induced migrasome formation (non-canonical migracytosis) in NRK cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Male C57BL/6 mice were fed a high-fat diet (HFD) to induce insulin resistance. During the last 12 weeks of the 16-week HFD feeding period, the mice were treated daily with Ly93 (20mg/kg and 40mg/kg) via intragastric administration (i.g.). A normal diet (ND) group served as the control. |
Dosage form | 20mg/kg and 40mg/kg; i.p.; Once daily for 12 weeks. |
Applications | Ly93 administration significantly improved high-fat diet-induced insulin resistance. Ly93 reduced fasting blood insulin (Fins) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) index, and enhanced insulin tolerance. Ly93 also increased glycogen content in the liver and skeletal muscle, and upregulated the phosphorylation of key insulin signaling proteins (IRS-1, Akt, and GSK-3β) in liver tissue. |
References: | |
| Cas No. | 1883528-69-5 | SDF | Download SDF |
| 分子式 | C 21H 20N 2O 2 | 分子量 | 332.4 |
| 溶解度 | DMSO : 250 mg/mL (752.11 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0084 mL | 15.0421 mL | 30.0842 mL |
| 5 mM | 601.7 μL | 3.0084 mL | 6.0168 mL |
| 10 mM | 300.8 μL | 1.5042 mL | 3.0084 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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