AZD7687

AZD7687 is a potent and selective DGAT1 inhibitor with an IC50 value of 80 nM (hDGAT1).IC50 value: 80 nM [1]Target: DGAT1in vitro: Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity. AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship [2].in vivo: 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 TAG were demonstrated with AZD7687 doses ≥5mg compared with placebo (p<0.01). Significant (p<0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at the end of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea [3].

Signaling Pathways >> Metabolic Enzyme/Protease >> Acyltransferase

Research Areas >> Metabolic Disease

[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

[2]. Denison H, 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.

[3]. 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.

Avasimibe | LCQ-908 | DGAT-3 | A922500 | Xanthohumol | PF-04620110 | MGAT2-IN-1 | DGAT-1 inhibitor 2 | DGAT1-IN-1 | K-604 dihydrochloride | PF-06471553 | YM17E | ABT-046 | RP 70676 | Furan-2-carboxylic acid