产品说明书

FG 2216

Print
Chemical Structure| 223387-75-5 同义名 : IOX3;YM311
CAS号 : 223387-75-5
货号 : A181287
分子式 : C12H9ClN2O4
纯度 : 99%+
分子量 : 280.664
MDL号 : MFCD23136998
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(178.15 mM)，配合低频超声助溶，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：
生物活性
靶点

  • PHD2

    PHD2, IC50:3.9 μM
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. FG-2216 is the PHD inhibitor with IC50 value of 3.9μM for PHD2 (measure by SAR study). Treatment with FG-2216 for 24h can stabilize HIF-1α and HIF-2α in Hep3B cells. Significant increase of EPO, as well as obvious band of HIF-1α and HIF-2α can be observed in Hep3B cells treated with 100μM FG-2216 for 24h[1]. Pre-treatment with FG-2216 at dose of 25 or 50mg/kg, b.w., i.p., 6h prior to initiation of ischaemia, caused HIF-1α and HIF-2α accumulation in kidney of rats, accompanied with increased transcriptional level of HIF targeted gene EPO and Glut-1[2]. FG-2216 increased hemoglobin in healthy volunteers and hemodialysis patients with CKD in a phase IIa study. Thus, it was regarded as the lead drug candidate for the treatment of CKD-related anaemia[3].
作用机制 FG-2216 can bind with the catalytically active domain of human PHD2 and fill the empty spaces with hydrophobic functional groups.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293 cells Function assay Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolin, IC50=3.5 nM 23844574
Hep3B cells Function assay Inhibition of PHD2 in human Hep3B cells assessed as erythropoietin secretion by ELISA, IC50=3.9 μM 24894560
Hep3B cells 100 uM Function assay 24 h Inhibition of PHD2 in human Hep3B cells assessed as increase in erythropoietin secretion at 100 uM after 24 hrs by ELISA 24894560
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.56mL

0.71mL

0.36mL

17.82mL

3.56mL

1.78mL

35.63mL

7.13mL

3.56mL
参考文献

[1]Hong YR, Kim HT, et al. [(4-Hydroxyl-benzo[4,5] thieno[3,2-c] pyridine-3-carbonyl)-amino] -acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7.

[2]Wang Z, Schley G, et al. The protective effect of prolyl-hydroxylase inhibition against renal ischaemia requires application prior to ischaemia but is superior to EPO treatment. Nephrol Dial Transplant. 2012 Mar;27(3):929-36.

[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]Hsieh MM, Linde NS, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. Blood. 2007;110(6):2140-7.