A922500
(Synonyms: DGAT-1抑制剂,A-922500, A 922500) 目录号 : GC15614
A diacylglycerol acyltransferase 1 inhibitor
Cas No.:959122-11-3
Sample solution is provided at 25 µL, 10mM.
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A922500 is a potent, active, selective and orally bioavailable inhibitor of diacylglycerol acyltransferase-1 (DGAT-1). It is a small molecular with the formula of C26H24N2O4 and molecular weight of 428.48. A922500 inhibits human DGAT-1 with an IC50 value of 9 nM, but does not inhibit other acyltransferases, such as DGAT-2, ACAT-1 and ACAT-2. [1] Diacylglycerol acyltransferase (DGAT) catalyzes esterification of 1,2-diacylglycerol (DAG) with fatty acyl-CoA to form triglycerides (TG) at the endoplasmic reticulum.[2]
Reference
[1] Andrew J. K, Jason A. S, Kelly J. L, Andrew J. S, Philip R. K, Regina M. R, et al. In vivo efficacy of acyl CoA: Diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. European Journal of Pharmacology. 2010, 637. 155-161.
[2] Kyeong L, Ja-Il G, Hwa Young J, Minkyoung K, Shanthaveerappa K. B, et al. Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2012, 22. 7456–7460.
| Cell experiment [1,2]: | |
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Cell lines |
HepG2 hepatoma cells |
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Preparation method |
The solubility of this compound in DMSO is > 21.25 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 μM, 60 min |
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Applications |
In HepG2 cell lysates, A-922500 (1 μM) inhibited about 99% of recombinant DGAT1 enzymatic activity. Exposure of HepG2 cells to A-922500 dose-dependently inhibited TG synthesis (stable isotope-labeled triolein; 13C18-oleoyl, 13C18-oleoyl, 13C18-oleoyl). In HEK293 cells expressing DGAT1, A-922500 inhibited [13C18]oleoyl triolein incorporation with the IC50 values of 17 nM. |
| Animal experiment [3-5]: | |
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Animal models |
Zucker fatty rats and diet-induced dyslipidemic hamsters, DIO mice, DGAT-1(-/-) mice, |
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Dosage form |
oral gavage |
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Application |
In Zucker fatty rats and diet-induced dyslipidemic hamsters, oral administration of A 922500 (3 mg/kg, 14 days) significantly reduced serum triglycerides and free fatty acid levels. A 922500 (3 mg/kg) significantly increased high-density lipoprotein-cholesterol. In DIO mice, A 922500 induced weight loss and reduced liver triglycerides when dosed chronically. A 922500 depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice. A 922500 (0.03, 0.3 and 3 mg/kg, p.o.) dose-dependently attenuated the maximal postprandial rise in serum triglyceride concentrations. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Qi J, Lang W, Geisler J G, et al. The use of stable isotope-labeled glycerol and oleic acid to differentiate the hepatic functions of DGAT1 and-2. Journal of lipid research, 2012, 53(6): 1106-1116. [2]. Qi J, Lang W, Giardino E, et al. High-content assays for evaluating cellular and hepatic diacylglycerol acyltransferase activity. Journal of lipid research, 2010, 51(12): 3559-3567. [3]. Zhao G, et al. Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor. J Med Chem. 2008, 51(3), 380-383. [4]. King, Andrew J.; Segreti, Jason A.; Diacylglycerol acyltransferase 1 inhibition lowers serum triglycerides in the Zucker fatty rat and the hyperlipidemic hamster. Journal of Pharmacology and Experimental Therapeutics (2009), 330(2), 526-531. [5]. King AJ, Segreti JA, Larson KJ, Souers AJ, Kym PR, Reilly RM, Collins CA, Voorbach MJ, Zhao G, Mittelstadt SW, Cox BF.In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia.Eur J Ph |
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| 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 | 0.4668 mL | 2.3338 mL | 4.6677 mL |
| 10 mM | 0.2334 mL | 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet