生物活性

• 描述The family of HIF-PH (HIF prolyl hydroxylase) enzymes are the main molecular to regulate HIF activity through hydroxylation at 2 proline residues and cause the degradation of HIF, thus leading to inhibition on accumulation of functional HIF under normoxia. Roxadustat (FG-4592) is the second generation HIF-PH inhibitor. Treatment with FG-4592 on dose of 5 - 50 μM can stabilize HIF-1α and inhibit apoptosis in tert-Butylhydroperoxide-stimulated PC12 cells. Intraperitoneal injection with FG-4592, 50 mg/kg/day, showed neuroprotection against spinal cord injury through stabilization of HIF-1α in SCI (Traumatic spinal cord injury) mice model^[1]. FG-4592 (50 μM) can increase HiPO4-induced mineralization through up-regulation of HIF-1α levels in vascular smooth muscle cells^[2]. For Roxadustat can induce elevations in endogenous EPO levels and hemoglobin levels, it is now used to treatment of anemia in chronic kidney disease^[3].
• 作用机制Most HIF-PH inhibitors are 2-oxogluarate derivatives, region of which can compete with HIF^[4].

• 动物研究
  剂量	Mice[5] (p.o.): 15 mg/kg - 60 mg/kg; rat: 2.5 mg/kg - 10 mg/kg
  给药途径	p.o.
  动物药代数据	Animal Mice[5] Rats[5] Dose 15 mg/kg 10 mg/kg Administration oral gavage oral gavage Cmax 40.1 ± 3.8 mg/ml 13.4 ± 0.41 mg/ml AUC0→t 127 ± 29 mg·h/ml 69.6 ± 3.9 mg·h/ml