LFHP-1c (C09-1142-437)

LFHP-1c is an PGAM5 inhibitor with neuroprotective activity in brain ischemic stroke. LFHP-1c protects blood-brain barrier integrity from ischemia-induced injury. LFHP-1c binds to endothelial PGAM5 to inhibit the activity of PGAM5 phosphatase and the interaction of PGAM5 with NRF2. LFHP-1c exhibits in vitro and in vivo protection.In VitroLFHP-1c (1, 2, or 5 μmol/L; 9 h) treatment, and followed by hypoxic treatment, increases NRF2 protein expression and facilitates nuclear translocation of NRF2 in primary rat brain microvascular endothelial cells (rBMECs). MCE has not independently confirmed the accuracy of these methods. They are for reference only. ImmunofluorescenceCell Line: Primary rat brain microvascular endothelial cells (rBMECs) Concentration: 2 μmol/L Incubation Time: 1 h Result: Bound to PGAM5, to facilitate nuclear translocation of NRF2.In VivoLFHP-1c (5 mg/kg; iv; 2 doses) prevents BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats . LFHP-1c (3 mg/kg, 1 mL/kg; iv; 8 doses) ameliorates brain ischemic injury in tMCAO model of M. fascicularis through PGAM5–NRF2 axis . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Nonhuman primate Macaca fascicularis model with tMCAO Dosage: 3 mg/kg, 1 mL/kg Administration: IV; at 4 h, 1, 2, 3, 4, 5, 6 and 7 days after tMCAO onset. Result: Reduced infarct volume, brain edema and neurological deficits in Transient MCAO model in M. fascicularis. Animal Model: SD rats (230-250 g) Dosage: 1 mg/kg, 5 mg/kg in 0.5 mL volume Administration: IV; injected at 4 or 12 h after ischemia onset, and then injected another time at 24 h post-ischemia Result: Dose-dependently protected rat brains against ischemia/reperfusion injury at 72 h after ischemia onset with a moderate therapeutic window. Prevented BBB disruption and attenuated endothelial inflammation in rat cerebral microvessels at 72 h after ischemia onset.Form:Solid. Specification: 0.97 Molecular Formula: C55H64N6O4 Molecular Weight: 873.13