Powder: -20°C for 3 years | In solvent: -80°C for 1 year
A-69412 (N-1-(Fur-3-ylethyl)-N-hydroxyurea) is a reversible, specific inhibitor of the hydrophilic 5-lipoxygenase. It has the potential to treat ulcerative colitis and asthma, and possibly other inflammatory and allergic conditions.
説明 | A-69412 (N-1-(Fur-3-ylethyl)-N-hydroxyurea) is a reversible, specific inhibitor of the hydrophilic 5-lipoxygenase. It has the potential to treat ulcerative colitis and asthma, and possibly other inflammatory and allergic conditions. |
ターゲット&IC50 | 5-LOX:1 μM, LTB4:1 μM |
In vitro | A-69412 inhibits the formation of 5-HETE by the 20000×g supernatant of RBL-I cells in a dose-dependent fashion. A-69412 also inhibits the formation of LTB4 in calcium ionophore A23187 stimulated human PMNL (IC50=8.9 μM). A-69412 is more potent in inhibiting LTB4 formation in ionophore-stimulated human whole blood. The potency of A-69412 in a number of assays using several donors consistently show activity in the low micromolar range (mean IC50=1.4 μM, range 0.5-3 μM, 9 donors), several-fold more potent than its activity in the other in vitro assays[1]. |
In vivo | Oral administration of A-69412 effectively inhibits leukotriene production across various species, demonstrating its potent, long-acting nature. In rats, A-69412 exhibits strong inhibition of leukotriene formation with an oral effective dose (ED50) of 5 mg/kg. Similarly, in dogs, a single dose of 5 mg/kg ensures nearly complete leukotriene inhibition for up to 16 hours, with plasma concentrations measuring 38 μM at 0.5 hours post-dose and reducing to 5 μM at 16 hours. These results align with ex vivo observations of 100% inhibition at 0.5 hours and 90% at 16 hours post-dosing. Moreover, A-69412 outperforms zileuton in cynomolgus monkeys, maintaining over 50% inhibition of LTB4 biosynthesis for 8 hours compared to zileuton's effectiveness within just the first 2 hours post-dosing. In rat models of anaphylactic reaction, oral A-69412 dose-dependently curbs leukotriene production in the peritoneal cavity, with blood levels ranging between 4 to 100 μM for doses of 2 to 50 mg/kg. Remarkably, A-69412 continues to significantly inhibit leukotriene production when administered up to 8 hours before the antigen challenge, with plasma concentrations ranging from 44 μM at 0.5 hours to 10 μM at 8 hours post-dosing[1]. |
動物実験 | A-69412 is suspended in 0.2% methylcellulose with a Potter-Elvehjem homogenizer equipped with a Teflon-coated pestle and administered orally (20 mg/kg) to beagle dogs, cynomolgus monkeys, and male SD rats. Zileuton is used for comparison. All animals are fasted overnight before dosing but allowed water ad libitum. Heparinized blood samples are obtained before and at various times after compound administration in the dog and monkey studies. Groups of rats are dosed with vehicle or A-69412 and 1 h and 15 min later, the animals are sacrificed and blood collected by cardiac puncture into heparinized syringes. Aliquots of blood from all the three species are incubated at 37°C with 50 μM calcium ionophore, A23187. After 30min, the blood is placed in an ice bath and analyzed for LTB4. |
別名 | N-1-(Fur-3-ylethyl)-N-hydroxyurea |
分子量 | 170.17 |
分子式 | C7H10N2O3 |
CAS No. | 123606-23-5 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 45 mg/mL (264.44 mM)
You can also refer to dose conversion for different animals. 詳細
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A-69412 123606-23-5 Metabolism Lipoxygenase A 69412 A69412 N-1-(Fur-3-ylethyl)-N-hydroxyurea Inhibitor inhibitor inhibit