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AZD7687

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Chemical Structure| 1166827-44-6 同义名 : -
CAS号 : 1166827-44-6
货号 : A875906
分子式 : C21H25N3O3
纯度 : 98+%
分子量 : 367.442
MDL号 : MFCD23098776
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(136.08 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the final step in triacylglycerol (TAG) assembly, is suggested as a treatment for type 2 diabetes and obesity based on animal data indicating insulin sensitization and weight reduction[3]. AZD7687 is a potent and selective DGAT1 inhibitor with an IC50 value of 80 nM to human DGAT1recombinant. In in vitro radioligand binding and enzyme assays, AZD7687 showed inhibition of acyl-CoA: cholesterol acetyltransferase (79% at 10μM), fatty acid amide hydrolase (IC50=3.7μM), muscarinic M2 receptor (IC50=80.5μM), and phosphodiesterase PDE10A1 (IC50=5.5μM). In the rat oral lipid tolerance test (OLTT) assay, AZD7687 was able to reduce the formation of TAG (triacylglycerol) in adipose tissue (measured as TAG/DAG ratio) in an exposure dependent manner. In addition, AZD7687 was shown to have beneficial effects in several preclinical metabolic disease models (e.g., enhanced GLP-1 secretion, delayed gastric emptying, reduced food intake, improved insulin sensitivity, reduced atherosclerosis)[4]. Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1 week. Dose-dependent reductions in postprandial serum triacylglycerol (TAG) were demonstrated with AZD7687 doses ≥5 mg compared with placebo (p < 0.01)[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.72mL

0.54mL

0.27mL

13.61mL

2.72mL

1.36mL

27.22mL

5.44mL

2.72mL
参考文献

[1]Denison H, Nilsson C, et al. Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first-time-in-human single-dose study. Diabetes Obes Metab. 2013 Feb;15(2):136-43.

[2]Barlind JG, Bauer UA, et al. Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687). J Med Chem. 2012 Dec 13;55(23):10610-29.

[3]Denison H, Nilsson C, Kujacic M, Löfgren L, Karlsson C, Knutsson M, Eriksson JW. Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first-time-in-human single-dose study. Diabetes Obes Metab. 2013 Feb;15(2):136-43. doi: 10.1111/dom.12002. Epub 2012 Sep 30. PMID: 22950654.

[4]Barlind JG, Bauer UA, Birch AM, Birtles S, Buckett LK, Butlin RJ, Davies RD, Eriksson JW, Hammond CD, Hovland R, Johannesson P, Johansson MJ, Kemmitt PD, Lindmark BT, Morentin Gutierrez P, Noeske TA, Nordin A, O'Donnell CJ, Petersson AU, Redzic A, Turnbull AV, Vinblad J. Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687). J Med Chem. 2012 Dec 13;55(23):10610-29. doi: 10.1021/jm301296t. Epub 2012 Nov 21. PMID: 23116186.

[5]Denison H, Nilsson C, Löfgren L, Himmelmann A, Mårtensson G, Knutsson M, Al-Shurbaji A, Tornqvist H, Eriksson JW. Diacylglycerol acyltransferase 1 inhibition with AZD7687 alters lipid handling and hormone secretion in the gut with intolerable side effects: a randomized clinical trial. Diabetes Obes Metab. 2014 Apr;16(4):334-43. doi: 10.1111/dom.12221. Epub 2013 Oct 31. PMID: 24118885.