Dorsomorphin (Compound C) dihydrochloride

生物活性

Dorsomorphin（BML-275）二盐酸盐是一种有效的，可逆的AMPK选择性抑制剂，K_i为109 nM，Dorsomorphin还对BMP有抑制作用。BML-275二盐酸盐对AMPK活性的抑制几乎完全抑制了HT-29细胞中的自体吞噬的蛋白质水解作用。此外，BML-275二盐酸盐选择性抑制BMP I型受体ALK2，ALK3和ALK6，并因此阻断BMP介导的SMAD1/5/8磷酸化作用，靶点基因转录和成骨分化。Dorsomorphin (10 毫克/千克)在成年小鼠体内，降低肝杀菌肽表达的基础水平，并增加血清中铁离子浓度。Dorsomorphin (0.2 毫克/千克，静脉注射)显著减少LPS 处理的大鼠胸主动脉中VCAM-1 和 ICAM-1的表达。

使用AbMole产品发表的文献

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产品使用成果展示

	数据来源	Hum Mol Genet (2016). Figure 2. Dorsomorphin dihydrochloride
	方法	RT-qPCR
	细胞系/动物模型	iPSC lines
	浓度	1 μM
	处理时间	72 h
	实验结果	We generated cortical neurons using a well-established protocol with small molecule dual SMAD inhibition for neural induction followed by plating of neuroepithelial cells for final differentiation

实验参考

体外实验*
细胞系	Spermatogonial Cell
方法	Dorsomorphin was added to the medium at a final concentration of 0, 1, 2, 4, or 8 µM (in final 0.4% dimethyl sulfoxide). The cells were maintained at 28.5°C in an atmosphere of 3% carbon dioxide and the medium was replaced every 3–4 days.
浓度	0, 1, 2, 4, or 8 µM
处理时间	3 weeks

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	C57BL/6 mice
配制	DMSO
剂量	10 mg/kg
给药处理	i.p.

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	472.41
分子式	C24H25N5O.2HCl
CAS号	1219168-18-9
溶解性（25°C）	Water 45 mg/mL DMSO 5 mg/mL (Need ultrasonic)
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.1168 mL	10.584 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

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Wong TT, et al. PLoS One. Dorsomorphin promotes survival and germline competence of zebrafish spermatogonial stem cells in culture.

[2] Hyeon Ung Park, et al. Mol Cancer Ther. AMP-activated protein kinase promotes human prostate cancer cell growth and survival

[3] Yu PB, et al. Nat Chem Biol. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism.