产品描述:
TS-011 is an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis.{61913} It inhibits 20-HETE synthesis in human and rat renal microsomes (IC50s = 8.42 and 9.19 nM, respectively), as well as by the cytochrome P450 (CYP) isoforms CYP4F2, CYP4F3A, CYP4F3B, and CYP4A11 in cell-free assays (IC50s = 30.4, 42.6, 43.0, and 188 nM, respectively). It is selective for these CYPs over CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (IC50s = >60 µM for all), as well as a panel of receptors and other enzymes at 1 µM. TS-011 (0.01-1 mg/kg, i.v.) reverses decreases in cerebral blood flow and increases in cerebrospinal fluid 20-HETE levels in a rat model of subarachnoid hemorrhage. It also reduces infarct volume and prevents neurological deficits in a rat model of stroke induced by middle cerebral artery occlusion (MCAO).{61914}