| Bioactivity | AZD7687 is a potent, selective, reversible and orally active diacylglycerol acyltransferase 1 (DGAT1) inhibitor with an IC50 of 80 nM for human DGAT1. AZD7687 can be used for type 2 diabetes mellitus and obesity research[1][2]. | ||||||||||||
| Invitro | In an in vitro recombinant mouse, dog, and human DGAT1 enzyme assay, AZD7687 has an IC50 of approximately 100 nM, 60 nM, and 80 nM, respectively. AZD7687 (compound 30) shows inhibition of acyl-CoA:cholesterol acetyltransferase (79% at 10 μM), fatty acid amide hydrolase (IC50 = 3.7 μM), muscarinic M2 receptor (IC50 = 80.5 μM), and phosphodiesterase PDE10A1 (IC50 = 5.5 μM). No activity against human DGAT2 is detected[1][2]. | ||||||||||||
| In Vivo | Prolonged pharmacological inhibition of DGAT1 with AZD7687 in mice results in the same skin phenotype, including sebaceous gland atrophy and alopecia, as seen in the skin of DGAT1-/- mice. AZD7687-mediated effects on the skin were dose- and time-dependent and reversible[3]. | ||||||||||||
| Name | AZD7687 | ||||||||||||
| CAS | 1166827-44-6 | ||||||||||||
| Formula | C21H25N3O3 | ||||||||||||
| Molar Mass | 367.44 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Barlind JG, 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. [2]. Denison H, et al. 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. 2013 Oct 4. [3]. Eike Floettmann, et al. Pharmacological inhibition of DGAT1 induces sebaceous gland atrophy in mouse and dog skin while overt alopecia is restricted to the mouse. Toxicol Pathol. 2015 Apr;43(3):376-83. |