MK-8617

製品コードS8443 バッチS844303

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₁N₅O₄
	分子量	443.45	CAS No.	1187990-87-9
Solubility (25°C)*	体外	DMSO	21 mg/mL warmed with 50ºC water bath (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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
in vitro	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].
in vivo	Tritiated 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^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HEK293 cells
	濃度	15 & 30 μM
	反応時間	24 h
	実験の流れ	Cells were treated with various concentrations of MK-8617.
動物実験	動物モデル	C57Bl/6 mice
	投薬量	1 mg/kg po, 0.5 mg/kg iv
	投与方法	i.v or p.o

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。