| Description | DAAO inhibitor-1 is a potent D-amino acid oxidase (DAAO) inhibitor (IC50: 0.12 μM). |
| Cell experiments | Time courses of the unchanged pharmacons in hepatocytes and in hepatic microsomes were obtained. Each compound was incubated with cell suspension (2 × 10^6 cells/mL) or with microsomes (4 mg/mL) at 37 °C in a humid atmosphere containing 5% CO2. The parent compounds were added directly to the cell culture medium or to 0.1 M Tris-HCl buffer (pH 7.4) at the final concentration of 1 μM. The microsomal incubation mixtures contained an NADPH-regenerating system (1 mM NADPH, 10 mM glucose 6–phosphate, 5 mM MgCl2 and 2 units/mL glucose 6-phosphate dehydrogenase). At various time points (at 0, 15, 30, 45, 60, 90, 120, 180, 240 min for hepatocyte incubations; at 0, 15, 30, 45, 60, 90 min for microsomal incubations), the incubation mixtures were sampled (aliquots: 0.25 mL) and terminated by the addition of 0.17 mL ice-cold acetonitrile containing the internal standard, carbamazepine (0.13 μM). The cell and microsomal debris was separated by centrifugation, and the supernatant was analyzed by LC-MS/MS for quantitation of the parent compound. |
| Animal experiments | Male NMRI mice of 25–30 g were housed in an air-conditioned (22 +/- 2 °C) animal room with 12 h light and dark cycle. They had free access to standard laboratory rodent chow and water. Five mice per group were treated intraperitoneally with 30 mg/kg D-serine in the absence or presence of 30 mg/kg DAAO inhibitor-1 dissolved in 5% DMSO containing saline. The test compound and D-serine were administered simultaneously. After 10, 20, 30, 60, 120, 240 and 360 min the mice were anesthetized by carbon dioxide, decapitated and their blood was collected using EDTA as anticoagulant. Plasma was obtained by centrifugation at 2000g, 4 °C for 5 min and the samples were stored frozen at -80 °C until analysis. |
| Target activity | DAAO:0.12 μM (cell free) |
| molecular weight | 152.13 |
| Molecular formula | C7H5FN2O |
| CAS | 2065250-25-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 125 mg/mL (821.67 mM), Sonication is recommended. |
| References | 1. Szilágyi B, et al. Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors. Bioorg Med Chem. 2018 May 1;26(8):1579-1587. |