A922500
(Synonyms: DGAT-1抑制剂,A-922500, A 922500) 目录号 : GC15614
A922500是一种有效、选择性高且具有口服活性的二酰基甘油酰基转移酶1（DGAT-1）抑制剂，对人源和小鼠DGAT-1的IC50值分别为9和22nM。
Cas No.:959122-11-3
Sample solution is provided at 25 µL, 10mM.
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A922500 is a potent, selective, and orally bioavailable diacylglycerol acyltransferase 1 (DGAT-1) inhibitor with IC50 values of 9 and 22nM against human and mouse DGAT-1, respectively[1]. DGAT-1 is the key rate-limiting enzyme that catalyzes the final step of triglyceride synthesis by transferring fatty acyl groups to diacylglycerol to form triglycerides[2]. A922500 is usualy used in studies of type 2 diabetes, obesity, and lipid-metabolism disorders[3].
In vitro, A922500（10 or 50μM; 54 hpi to Day 8）reduces cytoplasmic lipid droplet area, increases mitochondrial activity and total cell number, and improves post-vitrification survival in bovine IVP blastocysts without affecting blastocyst yield[4].A922500 (40μM; 24h) reduced neutral lipid droplet formation and significantly decreased cell viability in HuH7 hepatocytes under non-toxic oleic acid loading[5].
In vivo, A922500 (30mg/kg/day; 6 weeks; p.o.) reduced triglyceride content in bronchoalveolar lavage macrophages but did not decrease lung bacillary burden or inflammation in Mycobacterium tuberculosis-infected C3HeB/FeJ mice[6]. A922500 (3mg/kg; p.o.) reversed sepsis-induced hepatic lipid droplet accumulation, reduced AST/ALT levels, and suppressed lipid peroxidation markers 4-HNE and 3-NT in caecal ligation and puncture (CLP) mouse model[7].
References:
[1] King AJ, Segreti JA, Larson KJ, et al. Diacylglycerol acyltransferase 1 inhibition lowers serum triglycerides in the Zucker fatty rat and the hyperlipidemic hamster. J Pharmacol Exp Ther. 2009;330(2):526-531.
[2] Lee K, Goo JI, Jung HY, et al. Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. Bioorg Med Chem Lett. 2012;22(24):7456-7460.
[3] Tsuda N, Kumadaki S, Higashi C, et al. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice. PLoS One. 2014;9(11):e112027.
[4] Cañón-Beltrán K, Giraldo-Giraldo J, Cajas YN, et al. Inhibiting diacylglycerol acyltransferase-1 reduces lipid biosynthesis in bovine blastocysts produced in vitro. Theriogenology. 2020;158:267-276.
[5] Moliterni C, Vari F, Schifano E, et al. Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells. J Lipid Res. 2024;65(12):100692.
[6] Ruelas Castillo J, Guerrini V, Quijada D, et al. Pharmacologic Inhibition of Macrophage Triglyceride Biosynthesis Pathways Does Not Improve Mycobacterium tuberculosis Control in Infected Mice. J Infect Dis. 2025;231(5):1141-1149.
[7] Teixeira L, Pereira-Dutra FS, Reis PA, et al. Prevention of lipid droplet accumulation by DGAT1 inhibition ameliorates sepsis-induced liver injury and inflammation. JHEP Rep. 2023;6(2):100984.
A922500是一种有效、选择性高且具有口服活性的二酰基甘油酰基转移酶1（DGAT-1）抑制剂，对人源和小鼠DGAT-1的IC50值分别为9和22nM[1]。DGAT-1是催化甘油三酯合成最后一步的关键限速酶，通过将脂肪酰基转移到二酰基甘油上形成甘油三酯[2]。A922500常用于2型糖尿病、肥胖症和脂代谢紊乱等研究[3]。
在体外，A922500（10或50μM；受精后54h至第8天）可减少牛体外受精囊胚的细胞质脂滴面积，增强线粒体活性和总细胞数，并提高玻璃化冷冻后的存活率，且不影响囊胚形成率[4]。A922500（40μM；24h）在非毒性油酸负荷下可减少HuH7肝细胞的中性脂滴形成，并显著降低细胞活力[5]。
在体内，A922500（30mg/kg/天；6周；口服）可降低结核分枝杆菌感染的C3HeB/FeJ小鼠的支气管肺泡灌洗巨噬细胞中的甘油三酯含量，但未能减少肺部细菌负荷或炎症[6]。A922500（3mg/kg；口服）在盲肠结扎穿孔（CLP）小鼠模型中可逆转脓毒症诱导的肝脏脂滴积聚，降低AST/ALT水平，并抑制脂质过氧化标志物4-HNE和3-NT[7]。
| Cell experiment [1]: | |
Cell lines | Human hepatocellular carcinoma Huh-7 cells |
Preparation Method | Human hepatocellular carcinoma Huh-7 cells were maintained in Dulbecco's Modified Eagle Medium (DMEM) low glucose with 10% fetal bovine serum (FBS), 100U/ml penicillin, 100μg/ml streptomycin, and 2mM glutamine. Cells were cultured at 37°C with 5% partial pressure of CO2 in a humidified atmosphere. Oleic acid(OA) was dissolved in fatty-acid-free BSA at a final molar ratio of 2:1 fatty acids/BSA, close to the value observed in human serum, and diluted to a proper final concentration in DMEM just before cell treatments. Cells were treated with BSA, or 200μM OA, 200μM OA + 40μM A922500 for 24h. Oil Red O (ORO) and BODIPY stain protocols were used for LD analysis. Following fatty acid treatments, HuH-7 cells were washed with PBS, fixed with 4% paraformaldehyde in PBS pH 7.4 for 20min, at room temperature, and stained with 0.5% ORO solution in isopropanol for 1h. After PBS washing, the LD number and area were quantified. |
Reaction Conditions | 40μM; 24h |
Applications | A922500 reduced neutral lipid droplet formation and significantly decreased cell viability in HuH7 hepatocytes under non-toxic oleic acid loading. |
| Animal experiment [2]: | |
Animal models | Female C57BL/6J mice |
Preparation Method | 8–12 weeks Female C57BL/6J mice were maintained on a standard rodent diet with ad libitum access to water under a 12h light/dark cycle and controlled temperature (23±1°C). Sepsis was induced by caecal ligation and puncture (CLP) . The number of punctures performed was varied according to the degree of severity sought, with either two perforations (moderate sepsis) or nine perforations (severe sepsis) made using a 22-gauge needle. Sham-operated animals underwent identical laparotomy but without ligation and punctures. At 6h and 24h postsurgery, sham and CLP mice were orally treated with 3mg/kg A922500. Animals were monitored for 48h for survival, clinical score, and body temperature analysis. The clinical evaluation was based on a multifactorial SHIRPA protocol. Blood and liver tissues were collected for further analysis. |
Dosage form | 3mg/kg; p.o. |
Applications | A922500 (3mg/kg; p.o.) reversed sepsis-induced hepatic lipid droplet accumulation, reduced AST/ALT levels, and suppressed lipid peroxidation markers 4-HNE and 3-NT in caecal ligation and puncture (CLP) mouse model. |
References: | |
| Cas No. | 959122-11-3 | SDF | |
| 别名 | DGAT-1抑制剂,A-922500, A 922500 | ||
| 化学名 | (1R,2R)-2-[4-[4-(phenylcarbamoylamino)phenyl]benzoyl]cyclopentane-1-carboxylic acid | ||
| Canonical SMILES | C1CC(C(C1)C(=O)O)C(=O)C2=CC=C(C=C2)C3=CC=C(C=C3)NC(=O)NC4=CC=CC=C4 | ||
| 分子式 | C26H24N2O4 | 分子量 | 428.48 |
| 溶解度 | ≥ 21.25mg/mL in DMSO | 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 | 2.3338 mL | 11.6692 mL | 23.3383 mL |
| 5 mM | 466.8 μL | 2.3338 mL | 4.6677 mL |
| 10 mM | 233.4 μL | 1.1669 mL | 2.3338 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。
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Quality Control & SDS
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- Purity: >98.50%
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