SB 204990
目录号 : GC16952
SB 204990是一种内酯前药，能够有效抑制ATP柠檬酸裂解酶活性。
Cas No.:154566-12-8
Sample solution is provided at 25 µL, 10mM.
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SB 204990, a lactone prodrug, potently inhibits ATP citrate-lyase [1]. SB 204990 reduces plasma cholesterol levels and triglyceride levels in animals by inhibiting ATP citrate lyase[2]. SB 204990 has been widely used in animal models to regulate the renal dysfunction induced by obesity and type 2 diabetes[3].
In vitro, SB 204990 treatment for 24 hours effectively inhibited the replication of SARS-CoV-2 WT, Delta, and Omicron variants in Caco2 cells, with IC50 values of 15.7µM, 13.1µM and 11.7µM, respectively[4]. SB 204990 treatment (40µM) for 24h significantly inhibited MDA-MB-231 cell viability in a glutamine-deficient medium[5]. Treatment with 100µM SB 204990 for 48 hours reversed galactose-induced β-Catenin activity and inhibited MC3T3 E1 cell differentiation into osteoblasts[6]. Treatment with 30µM SB 204990 for 48 hours inhibited TGF-β-stimulated proliferation and fibrin expression in cultured human cardiac fibroblasts (HCFs), reduced H3K9 and H3K27 acetylation [7].
In vivo, SB 204990 treatment via intraperitoneal injection at a dose of 135mg/kg/day for 14 days markedly reduced tumor growth in nude mice carrying xenografts of mouse pancreatic ductal cell lines bearing oncogenic K-rasG12D alleles[8]. Oral administration of SB 204990 at a dose of 250mg/kg/day for 15 weeks significantly improved metabolic status and physical health in high-fat diet (HFD)-fed C57BL/6 mice[9].
References:
[1] Pearce N J, Yates J W, Berkhout T A, et al. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids[J]. Biochemical Journal, 1998, 334(1): 113-119.
[2] van Vlijmenº B J M, Pearce N J, Bergö M, et al. Apolipoprotein E* 3-Leiden transgenic mice as a test model for hypolipidaemic drugs[J]. 1998.
[3] Li Y C, Chen Y, Deb D K. ATP‐Citrate Lyase is an Epigenetic Regulator to Promote Nephropathy in Obesity and Type 2 Diabetes[J]. The FASEB Journal, 2018, 32: 720.2-720.2.
[4] Yuen T T T, Chan J F W, Yan B, et al. Targeting ACLY efficiently inhibits SARS-CoV-2 replication[J]. International Journal of Biological Sciences, 2022, 18(12): 4714.
[5] Hatipoglu A, Menon D, Levy T, et al. Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells[J]. PLoS One, 2022, 17(10): e0276579.
[6] Busch M, White N, Shum L, et al. Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation[J]. Journal of Biological Chemistry, 2018, 293(41): 16019-16027.
[7] Kuwahara N, Nagao M, Shinohara M, et al. ACLY Promotes Cardiac Fibrosis via the Regulation of DNL and Histone Acetylation[J]. Hypertension, 2025, 82(6): 1116-1128.
[8] Hatzivassiliou G, Zhao F, Bauer D E, et al. ATP citrate lyase inhibition can suppress tumor cell growth[J]. Cancer cell, 2005, 8(4): 311-321.
[9] Sola-García A, Cáliz-Molina M Á, Espadas I, et al. Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging[J]. Communications biology, 2023, 6(1): 250.
SB 204990是一种内酯前药，能够有效抑制ATP柠檬酸裂解酶活性[1]。SB 204990通过抑制ATP柠檬酸裂解酶，可降低动物体内的血浆胆固醇和甘油三酯水平[2]。SB 204990已广泛应用于调节肥胖及2型糖尿病引发的肾功能障碍的动物模型中[3]。
在体外，SB 204990处理24小时能有效抑制SARS-CoV-2野生株、Delta和Omicron变异株在Caco2细胞中的复制，IC50值分别为15.7µM、13.1µM和11.7µM[4]。在谷氨酰胺缺乏培养基中，使用40µM的SB 204990处理MDA-MB-231细胞24小时可显著抑制细胞活力[5]。用100µM的SB 204990处理MC3T3-E1细胞48小时，能够逆转半乳糖诱导的β-Catenin活性升高，并抑制MC3T3-E1细胞向成骨细胞分化[6]。以30µM的SB 204990处理培养的人心脏成纤维细胞(HCFs)48小时，可抑制TGF-β刺激的细胞增殖和纤维蛋白表达，同时降低H3K9和H3K27的乙酰化水平[7]。
在体内，通过每日腹腔注射135mg/kg/day剂量的SB 204990连续14天，能显著抑制携带致癌K-rasG12D等位基因的小鼠胰腺导管细胞移植瘤在裸鼠体内的生长[8]。每日口服250mg/kg/day剂量的SB 204990连续15周，可显著改善高脂饮食(HFD)喂养的C57BL/6小鼠的代谢状态和身体健康水平[9]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 cells |
Preparation Method | MDA-MB-231 cells were cultured in glutamine-free DMEM supplemented with 10% fetal bovine serum (FBS). A total of 5×104 cells/500μl/well were seeded in 24-well plates. After 24 hours, cells were added to treatment medium containing 40μM SB 204990 or vehicle only and incubated at 37°C in 5% CO2, for 12 hours, 24 hours, 48 hours, and 96 hours, respectively. Cells were treated with 125μl XTT for 2h. Then, the samples were analyzed at a wavelength of 450nm. |
Reaction Conditions | 40µM; 12, 24, 48, and 96h |
Applications | SB 204990 significantly inhibited the viability of MDA-MB-231 cells in a time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Athymic nude female mice |
Preparation Method | Mouse pancreatic duct cells bearing oncogenic K-rasG12D alleles were resuspended in PBS at a concentration of 5×107 cells/ml. Tumors were established in athymic nude female mice (8-10 weeks of age) by subcutaneous injection of a 200μl volume of 1×107 cells. Mice with similar tumor sizes were randomly divided into two groups 3-5 weeks after tumor cell injection: an untreated group (injected with vehicle only) and a treated group (injected with SB 204990). Mice were monitored daily until treatment was completed. Body weight and tumor size were measured every 2-3 days. Tumor growth was recorded by measuring (with calipers) the two vertical diameters of the tumor. Tumor mass was calculated by equation 1/2(a×b2), where a is the long diameterand b is the short diameter. Treated mice were intraperitoneally injected with SB 204990 at a dose of 135mg/kg/day for 14 days. |
Dosage form | 135mg/kg/day for 14 days; i.p. |
Applications | SB 204990 treatment remarkably reduced tumor growth in nude mice carrying xenografts of mouse pancreatic ductal cells. |
References: | |
| Cas No. | 154566-12-8 | SDF | |
| 化学名 | 2-((3S,5R)-5-(6-(2,4-dichlorophenyl)hexyl)-3-hydroxy-2-oxotetrahydrofuran-3-yl)acetic acid | ||
| Canonical SMILES | ClC1=CC(Cl)=C(C=C1)CCCCCC[C@](O2)([H])C[C@](C2=O)(O)CC(O)=O | ||
| 分子式 | C18H22Cl2O5 | 分子量 | 389.27 |
| 溶解度 | DMF: 30 mg/ml,DMF:PBS(pH7.2) (1:2): 0.33 mg/ml,DMSO: 20 mg/ml,Ethanol: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5689 mL | 12.8446 mL | 25.6891 mL |
| 5 mM | 513.8 μL | 2.5689 mL | 5.1378 mL |
| 10 mM | 256.9 μL | 1.2845 mL | 2.5689 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
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