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别名 | N/A | 储存条件 (自收到货起) |
3年 / -20°C / 粉状 1年 / -80°C / 溶于溶剂 |
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化学式 | C24H21N5O4 |
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分子量 | 443.45 | CAS号 | 1187990-87-9 | |
Solubility (25°C)* | 体外 | DMSO | 21 mg/mL (47.35 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
产品描述 | MK-8617是一种具有口服活性的Hypoxia-inducible factor prolyl hydroxylase 1−3 (HIF PHD1−3)泛抑制剂,抑制PHD1, 2, 3 的IC50s分别为1.0, 1.0 和 14 nM。 | ||||||
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体外研究 | MK-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[1]. |
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体内研究 | Tritiated MK-8617 exhibited 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 showed 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) caused 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) caused 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[1]. |
动物实验 | 动物模型 | C57Bl/6 mice |
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剂量 | 1 mg/kg po, 0.5 mg/kg iv | |
给药处理 | i.v 或 p.o |
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MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y14 pathway [ PeerJ, 2023, 11:e15591] | PubMed: 37404479 |
Pro70 Hydroxylation of Actin Impairs Cell Motility Through Binding with VHL and Blocking His73 Methylation [ bioRxiv, 2021, 10.1101/2021.08.26.456853] | PubMed: None |
HIF hydroxylase inhibitors decrease cellular oxygen consumption depending on their selectivity. [ FASEB J, 2020, 34(2):2344-2358] | PubMed: 31908020 |
The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway [ FASEB J, 2019, 33(11):12630-12643] | PubMed: 31451021 |
Hypoxia-inducible factor-prolyl hydroxylase inhibitor ameliorates myopathy in a mouse model of chronic kidney disease. [ Am J Physiol Renal Physiol, 2019, 317(5):F1265-F1273] | PubMed: 31588798 |
特定的存储和包装每个产品的信息在产品说明书上都有注明。大多数Selleck产品,在推荐的条件下存储可稳定保存两年。产品有时建议的储存温度不同,大多数建议储存在-20°C,抑制剂属于化学试剂,可在常温下运输储存两周左右。即使如此,我们保证产品的出货量将保持产品质量的条件下,一般都会放入冰袋。望阁下收到产品后,请按照产品数据表建议适当存储。
如果需要长期保存,请于零下二十度低温保存。禁止用于人体及治疗!
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