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Dorsomorphin 2HCl

AMPK抑制剂，Dorsomorphin dihydrochloride（BML-275 dihydrochloride）是一种有效，选择性和 ATP 竞争性的 AMPK 抑制剂，Ki 为109±16 nM。

目录号: PC15471 纯度: ≥98%

CAS No. :1219168-18-9

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中文名称	Dorsomorphin 2HCl
中文别名	6-[4-[2-(1-哌啶基)乙氧基]苯基]-3-(4-吡啶基)吡唑并[1,5-A]嘧啶二盐酸盐;BML-275HCl,物质C盐酸盐;Dorsomorphin 2HCl 抑制剂
英文名称	Dorsomorphin 2HCl
英文别名	Dorsomorphin Dihydrochloride;Dorsomorphin 2HCl;6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine,dihydrochloride;BML-275;Dorsomorphin dihydrochloride (Compound C, BML-275);6-[4-[2-(1-PIPERIDINYL)ETHOXY]PHENYL]-3-(4-PYRIDINYL)-PYRAZOLO[1,5-A]PYRIMIDINE DIHYDROCHLORIDE;BML-275 2HCl;BML275 dihydrochloride;BML-275 dihydrochloride;Compound C dihydrochloride;FD5027;S7306,BML-275,Compound C
Cas No.	1219168-18-9
分子式	C₂₄H₂₅N₅O^.₂[HCl]
分子量	472.41
包装储存	Sealed and stored at 4℃，, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

生物活性

Dorsomorphin dihydrochloride (BML-275 dihydrochloride; Compound C dihydrochloride) is a potent, selective and ATP-competitive AMPK inhibitor, with a K_i of 109 nM. Dorsomorphin dihydrochloride inhibits BMP pathway by targeting the type I receptors ALK2, ALK3, and ALK6. Dorsomorphin dihydrochloride induces autophagy.

性状

Solid

IC50 & Target[1][2]

AMPK

109 nM (Ki)

ACVR1

BMPR1A

ALK6

Autophagy

体外研究(In Vitro)

Dorsomorphin (compound C) (0-10 μM, 18 h) suppresses 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner but has little effect on tunicamycin-induced GRP78 promoter activity. Dorsomorphin (compound C) C also suppresses GRP78 promoter activity induced by glucose withdrawal. Dorsomorphin (compound C) has no effect on 2DG-induced PERK activation and reduces the both basal and 2DG-induced AMPK phosphorylation levels in HT1080 cells.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis

Cell Line:	Human fibrosarcoma HT1080 cells.
Concentration:	0-10 μM.
Incubation Time:	18 hours
Result:	Suppressed 2DG-induced GRP78 promoter activity in a dose-dependent manner and also suppressed GRP78 promoter activity induced by glucose withdrawal.

体内研究(In Vivo)

Dorsomorphin (compound C: 10 mg/kg, intravenously once) treatment leads to a 60% increase in total serum iron concentrations, reduces basal levels of hepcidin expression and increasing serum iron concentrations in adult mice.
Dorsomorphin (compound C: 0.2 mg/kg, i.v., 30 min before LPS injection) reduces ICAM-1 and VCAM-1 expression in LPS-injected rat aorta.
Dorsomorphin (compound C; 25 mg/kg; i.p. injection, in male BALB/c mice) treatment before lipopolysaccharide (LPS) injection significantly reduces lethality in contrast to animals treated with LPS challenge only.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Wild-type (WT) C57BL/6 adult mice that are fed a standard iron-replete diet express high levels of hepcidin.
Dosage:	10 mg/kg.
Administration:	Intravenously once.
Result:	Led to a 60% increase in total serum iron concentrations. Effective in reducing basal levels of hepcidin expression and increasing serum iron concentrations in adult mice.

Animal Model:	Male Sprague-Dawley rats, 8 weeks of age (body weight 230-250 g).
Dosage:	0.2 mg/kg.
Administration:	I.V., 30 min before LPS injection.
Result:	Reduced ICAM-1 and VCAM-1 expression in LPS-injected rat aorta.

Animal Model:	Male BALB/c mice at 6-7 weeks of age weighing 20-22 g
Dosage:	25 mg/kg
Administration:	Injection i.p.; 60 min before LPS challenge
Result:	Treatment of mice with 25 mg/kg before LPS injection significantly reduced lethality in contrast to animals treated with LPS challenge only.

运输条件

Room temperature or refrigerated transportation.

储存方式

Sealed and stored at 4℃，, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

参考文献

[1]. Zhou G, et al. Role of AMP-activated protein kinase in mechanism of action. J Clin Invest. 2001 Oct;108(8):1167-74. [Information]

[2]. Saito S, et al. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling. PLoS One. 2012;7(9):e45845. [Information]

[3]. Yu PB, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan;4(1):33-41. [Information]

[4]. Kim YM, et al. Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells 体外研究 and in vivo. Atherosclerosis. 2011 Nov;219(1):57-64. [Information]

[5]. Guo Y, et al. AMPK inhibition blocks ROS-NFκB signaling and attenuates endotoxemia-induced liver injury. PLoS One. 2014 Jan 24;9(1):e86881. [Information]

溶解度数据

体外研究:

H₂O : 50 mg/mL (105.84 mM; Need ultrasonic)

DMSO : 5 mg/mL (10.58 mM; Need ultrasonic)

配制储备溶液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.1168 mL	10.5840 mL	21.1681 mL
5 mM	0.4234 mL	2.1168 mL	4.2336 mL
10 mM	0.2117 mL	1.0584 mL	2.1168 mL

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

建议依照次序添加每种溶剂： PBS
Solubility: 20 mg/mL (42.34 mM); Clear solution; Need ultrasonic and warming and heat to 60°C

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产品使用指南

Data Sheet

1：一般建议：溶解度为Medlife测试数据，可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同批次产品溶解度各有差异，仅做参考，具体以实验方案为准。

2：储存条件：粉末-20°C一般情况可以保存3年，溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异，请细致阅读产品信息，并辅助参考相关文献描述。

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