Roxadustat

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Chemical Structure| 808118-40-3 同义名 : FG-4592; ASP1517
CAS号 : 808118-40-3
货号 : A336488
分子式 : C19H16N2O5
纯度 : 98+%
分子量 : 352.34
MDL号 : MFCD20040519
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(298.01 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 4 mg/mL clear

PO 0.5% CMC-Na 45 mg/mL suspension

生物活性
靶点

  • HIF
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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.84mL

0.57mL

0.28mL

14.19mL

2.84mL

1.42mL

28.38mL

5.68mL

2.84mL
参考文献

[1]Wu K, Zhou K, et al. Stabilization of HIF-1α by FG-4592 promotes functional recovery and neural protection in experimental spinal cord injury. Brain Res. 2016 Feb 1;1632:19-26.

[2]Mokas S, Larivière R, et al. Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification. Kidney Int. 2016 Sep;90(3):598-609.

[3]Locatelli F, Fishbane S, et al. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am J Nephrol. 2017;45(3):187-199.

[4]Small-molecule inhibitors of HIF-PHD2: a valid strategy to renal anemia treatment in clinical therapy

[5]Beck J, Henschel C, et al. Evaluation of the Carcinogenic Potential of Roxadustat (FG-4592), a Small Molecule Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase in CD-1 Mice and Sprague Dawley Rats. Int J Toxicol. 2017 Nov/Dec;36(6):427-439.