Dorsomorphin (Compound C) is a selective and ATP-competitive AMPK inhibitor (Ki=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin induces autophagy[1][2].
IC50 & Target[1][2]
AMPK
109 nM (Ki)
ALK2
ALK3
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[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[2]
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[3]. 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[4]. 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[5].
上海金畔生物科技有限公司 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[3].
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)[4].
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[5]
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.
分子量
399.49
Formula
C24H25N5O
CAS 号
866405-64-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zhou G, et al. Role of AMP-activated protein kinase in mechanism of action. J Clin Invest. 2001 Oct;108(8):1167-74.
[2]. Kim YM, et al. Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo. Atherosclerosis. 2011 Nov;219(1):57-64.
[3]. 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.
[4]. Guo Y, et al. AMPK inhibition blocks ROS-NFκB signaling and attenuates endotoxemia-induced liver injury. PLoS One. 2014 Jan 24;9(1):e86881.
[5]. Yu PB, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan;4(1):33-41.