A922500
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 428.48 |
| Cas No. | 959122-11-3 |
| Formula | C26H24N2O4 |
| Synonyms | A-922500, A 922500 |
| Solubility | ≥21.25 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | (1R,2R)-2-[4-[4-(phenylcarbamoylamino)phenyl]benzoyl]cyclopentane-1-carboxylic acid |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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 | |
| Description | A922500 is a potent, selective and orally bioavailable inhibitor of DGAT-1 with IC50 values of 7 nM and 24 nM for human and mouse DGAT-1, respectively. | |||||
| Targets | DGAT-1 | DGAT-1 | ||||
| IC50 | 7 nM (human) | 24 nM (mouse) | ||||
Quality Control & MSDS
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Chemical structure
