| Description | A 922500 (DGAT-1 Inhibitor 4a) is an inhibitor for human and mouse DGAT-1 with IC50 of 7 nM and 24 nM, respectively, good selectivity over related acyltransferases, hERG, and a panel of anti-targets. |
| In vitro | A 922500 inhibits the phylogenetic family members acyl coenzyme A cholesterol acyltransferase-1 and -2 with IC50 of 296 μM. [1] A 922500 potently inhibits huDGAT-1 and mseDGAT-1. [2] |
| In vivo | Zucker fatty rats and diet-induced dyslipidemic hamsters are dosed orally with A 922500 (0.03, 0.3, and 3 mg/kg) for 14 days. Serum triglycerides ae significantly reduced by the 3 mg/kg dose of A 922500 in both the Zucker fatty rat (39%) and hyperlipidemic hamster (53%). These serum triglyceride changes are accompanied by significant reductions in free fatty acid levels by 32% in the Zucker fatty rat and 55% in the hyperlipidemic hamster. In addition, high-density lipoprotein-cholesterol is significantly increases (25%) in the Zucker fatty rat by A 922500 administered at 3 mg/kg. [1] A 922500 confers weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depletes serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice. [2] A 922500 (0.03, 0.3 and 3 mg/kg, p.o.) dose-dependently attenuates the maximal postprandial rise in serum triglyceride concentrations. [3] |
| Target activity | DGAT-1 (mouse):24 nM, DGAT-1 (human):7 nM |
| Synonyms | A922500, (1R,2R)-2-[[4-[[(苯基氨基)羰基]氨基][1,1-联苯]-4-基]甲酰基]环戊烷羧酸, DGAT-1 Inhibitor 4a |
| molecular weight | 428.48 |
| Molecular formula | C26H24N2O4 |
| CAS | 959122-11-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 70 mg/mL (163.37 mM), Sonication is recommended. |
| References | 1. King AJ et al. J Pharmacol Exp Ther. 2009, 330(2), 526-531. 2. Zhao G, et al. J Med Chem. 2008, 51(3), 380-383. 3. King AJ, et al. Eur J Pharmacol. 2010, 637(1-3), 155-161. 4. Masouleh S K. Lipid droplet formation drives pathogenic ILC2 responses in airway inflammation . 5. Karagiannis F, Masouleh S K, Wunderling K, et al. Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation[J]. Immunity. 2020, 52(4): 620-634. e6. |
| Citations | 1. Masouleh S K. Lipid droplet formation drives pathogenic ILC2 responses in airway inflammation. Immunity. 2020 2. Karagiannis F, Masouleh S K, Wunderling K, et al. Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation. Immunity. 2020, 52(4): 620-634. e6. 3. Wang W, Qu Y, Wang X, et al.Genetic variety of ORF3a shapes SARS‐CoV‐2 fitness through modulation of lipid droplet.Journal of Medical Virology.2023 |