PMX 53
PMX 53 性质
| 密度 | 1.40±0.1 g/cm3(Predicted) |
|---|---|
| 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 溶解度 | 溶于二甲基亚砜 |
| 酸度系数(pKa) | 13.23±0.70(Predicted) |
| 水溶解性 | Soluble to 2 mg/ml in water |
PMX 53 用途与合成方法
IC50: 20 nM (Complement C5a receptor)
MrgX2
PMX-53 is a potent CD88 antagonist and inhibits C5a-induced neutrophil myeloperoxidase release and chemotaxis with IC
50
values of 22 nM and 75 nM, respectively.
PMX-53 (10 nM) inhibits C5a-induced Ca
2+
mobilization in HMC-1 cells, but at higher concentrations( ≥30 nM) it causes degranulation in LAD2 mast cells, CD34
+
cell-derived mast cells, and RBL-2H3 cells stably expressing MrgX2. Replacement of Trp with Ala and Arg with dArg abolishes the ability of PMX-53 to inhibit C5a-induced Ca
2+
mobilization in HMC-1 cells and to cause degranulation in RBL-2H3 cells expressing MrgX2.
PMX-53 (0.3-3 mg/kg; subcutaneous injection; once; male Wistar rats) treatment inhibits the hypernociception induced by zymosan-activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E2 and dopamine.
Local pretreatment of rats with PMX-53 (60-180 μg per paw) inhibits zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception.
Pharmacokinetic analyses have shown that PMX-53 (3D53) appears in the plasma within 5 min of oral administration (3 mg/kg) to rats, with peak blood levels of approximately 0.3 µM beingreached within 20 min The plasma elimination half-life wasapproximately 70 min in this case.
The non-acetylated version of PMX-53 (3D53) binds to isolated mouse neutrophils with a K
d
value of 30 nM (mouse C5a binds with a K
d
value of 0.3 nM) and inhibits mouse C5a-induced chemotaxis with an IC
50
value of 0.5 nM.
| Animal Model: | Adult male Wistar rats (weighing 180-200 g) injected with zymosan |
| Dosage: | 0.3 mg/kg, 1 mg/kg or 3 mg/kg |
| Administration: | Subcutaneous injection; once |
| Result: | Inhibited the hypernociception induced by zymosan-activated serum and C5a. |
