货号	规格	价格	上海	北京	珠海	重庆	武汉	购买数量
S55773-1ml促销	10mM in DMSO	￥720.00 ￥570.00 S55773-1ml ￥570.00 现货	9 9	-	-	-	-

货号

规格

价格

上海

北京

珠海

重庆

武汉

购买数量

S55773-1ml促销

10mM in DMSO

￥720.00 ￥570.00

产品描述：

HIF 调节剂;HIF Modulators;;InformationMK-8617 MK-8617 is an orally active pan-inhibitor of Hypoxia-inducible factor prolyl hydroxylase 1−3 (HIF PHD1−3), inhibiting PHD1 , 2 , 3 with IC50s of 1.0, 1.0 and 14 nM, respectively.TargetsPHD1 (Cell-free assay); PHD2 (Cell-free assay); PHD3 (Cell-free assay) 1 nM; 1 nM; 14 nMIn vitroMK-8617 is not a significant inhibitor of the cytochrome p450 enzymes in vitro (IC50), CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6, >60 μM, and is a moderate reversible inhibitor of CYP2C8 at 1.6 μM in vitro. MK-8617 is inactive when screened at 10 μM against a general panel of 171 radioligand binding and enzymatic assays.In vivoTritiated MK-8617 exhibits minimal metabolic turnover in liver microsomes (+NADPH) from rat, dog, and monkey (<10% turover) but significant turnover in human liver microsomes (34% turnover) after 60 min (10 μM compound, 1 mg/mL microsomal protein). In terms of its pharmacokinetic profile, MK-8617 shows good oral bioavailability across species (36−71%), with low clearance and volume of distribution. The compound still has a relatively long elimination half-life across preclinical species. In mice (C57Bl/6), single doses of 5 and 15 mpk po (n = 3) causes increases in circulating reticulocytes measured on both 3 and 4 days postcompound challenge. In rat (Sprague−Dawley), a single dose titration of 1.5, 5, and 15 mpk po (n = 5) causes a large increase in serum erythropoietin(EPO) levels of 1.7-, 8-, and 204-fold relative to vehicle, respectively. Increases in circulating reticulocytes are observed at 5 and 15 mg/kg 3 days after challenge and, with the 15 mg dose, at 4 days after challenge.

靶点：

IC50: 1 nM (PHD2)

体内研究：

氚化 MK-8617 在大鼠、狗和猴子的肝微粒体中表现出最小的代谢转换 (<10% 转换)，但在 60 分钟后 (10 μM MK-8617，1 mg/mL) 在人肝微粒体中表现出显著的转换 (34% 转换) 微粒体蛋白)。就其药代动力学特征而言，MK-8617 显示出良好的跨物种口服生物利用度 (36% 至 71%)，清除率和分布容积较低。MK-8617 处理 48 小时后，放射性的给药后恢复约为 26% 的胆汁、12% 的尿液和 38% 的粪便，表明约 38% 的 MK-8617 被吸收并消除到胆汁和尿液中与大鼠研究中观察到的口服生物利用度 (~36%) 一致。MK-8617 还可以引起促红细胞生成素 (EPO) 水平升高，小鼠 MED 在静脉注射时为 1.5 mpk。

参考文献：

1. Debenham JS, et al. Discovery of N-[Bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (MK-8617), an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3) for the Treatment of Anemia. J Med Chem. 2016 Dec 22;59(24):11039-11049.

保存条件：

-80℃（运输条件：冰袋低温运输）

配置溶液浓度参考：

	1mg	5mg	10mg
1 mM	2.255 ml	11.275 ml	22.55 ml
5 mM	0.451 ml	2.255 ml	4.51 ml
10 mM	0.226 ml	1.128 ml	2.255 ml
50 mM	0.045 ml	0.226 ml	0.451 ml

注意：

部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

参考文献

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