3-Methyladenine (3-MA) 3-甲基腺嘌呤

生物活性

3-Methyladenine是一种选择性PI3K抑制剂，作用于Vps34和PI3Kγ，IC50分别为25 μM和60 μM；永久抑制I型PI3K，但对III型PI3K的抑制是短暂的，也抑制自噬体的形成。3-MA对Vps34轻微的偏向性可能是由于Vps34中某个特异性的疏水环形结构可以环绕在3-MA的3-甲基基团外面造成的 。据报道对于正常培养和饥饿处理的癌细胞3-MA都能引起细胞死亡。3-MA还可以不通过抑制自吞噬来抑制细胞迁移和入侵，这表明3-MA 除了抑制自吞噬之外还有其它生物功能。现配现用

使用AbMole产品发表的文献

• Cancer Res. 2023 Jan 18;83(2):251-263.

  MEX3A mediates p53 degradation to suppress ferroptosis and facilitate ovarian cancer tumorigenesis

• Front Immunol. 2023 Mar 14;14:1120996.

  ROS-AMPK/mTOR-dependent enterocyte autophagy is involved in the regulation of Giardia infection-related tight junction protein and nitric oxide levels

• Food Science and Human Wellness. 2023 Jun 1.

  3-epi-betulinic acid 3-O-β-D-glucopyranoside (eBAG) induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

• Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec 2.

  Dihydromyricetin alleviates inflammatory bowel disease associated intestinal fibrosis by inducing autophagy through the PI3K/AKT/mTOR signaling pathway

• Infect Immun. 2023 Nov 16;91(11):e0010323.

  Effects of Trichinella spiralis and its serine protease inhibitors on autophagy of host small intestinal cells

• J Orthop Surg Res. 2023 Feb 22;18(1):129.

  Osteogenic effects of rapamycin on bone marrow mesenchymal stem cells via inducing autophagy

• J CLIN PHARM THER. 2023 Sep 26;Issue (9): 969-978.

  Molecular mechanism of artesunate attenuates the release of proinflammatory cytokines from macrophages

• Int J Ophthalmol. 2023 Sep 18;16(9):1456-1464.

  Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model

• CNS Neurosci Ther. 2022 Nov 24.

  Acupuncture promotes nerve repair through the benign regulation of mTOR-mediated neuronal autophagy in traumatic brain injury rats

• J Ethnopharmacol. 2022 Sep 15;295:115398.

  Yangjing Zhongyu decoction facilitates mitochondrial activity, estrogenesis, and energy metabolism in H2O2-induced human granulosa cell line KGN

• Evid Based Complement Alternat Med. 2022 Apr 6;2022:4445293.

  Zhenzhu Xiaoji Decoction Induces Autophagy and Apoptosis Cell Death in Liver Cancer Cells through AKT/mTOR and JAK2/STAT3 Signaling Pathway

• Oxid Med Cell Longev. 2021 Jun 14;2021:6662225.

  Impaired Autophagy Induced by oxLDL/ β 2GPI/anti- β 2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction

• BMC Cancer. 2021 Feb 25;21(1):195.

  Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study

• Int J Case Rep Orthop. 2021;3(2):129-134.

  Rapamycin's osteogenic effects on bone marrow mesenchymal stem cells through triggering autophagy

• Int J Neurosci. 2020 Mar 11;1-15.

  Autophagy-deficiency in Bone Marrow Mononuclear Cells From Patients With Myasthenia Gravis: A Possible Mechanism of Pathogenesis.

• Front Pharmacol. 2018 May 14;14;9:334.

  Resveratrol Sensitizes Carfilzomib-Induced Apoptosis via Promoting Oxidative Stress in Multiple Myeloma Cells

• Mol Immunol. 2017 Jul;87:132-140.

  IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway

• Int J Clin Exp Med. 2017;10(5):7553-7562.

  Combination of icotinib and wogonin induces apoptosis and autophagy to overcome acquired resistance in lung cancer harbouring EGFR T790M mutation

产品使用成果展示

	数据来源	Front Pharmacol (2018). Figure 6. 3-methyladenine (AbMole BioScience, Houston, TX, USA)
	方法	Intracellular ROS Production
	细胞系/动物模型	MM cells
	浓度	1 mmol/L
	处理时间	2 h
	实验结果	However, RSV/CFZ combination increased levels of LC3-II and p62/SQSTM1. Higher levels of LC3-II could be partially blocked by the autophagy inhibitor 3-MA, but not for p62/SQSTM1

	数据来源	Int J Clin Exp Med (2017) . Figure 6. 3-methyladenine (3-MA) (Abmole Bioscience Inc. Houston, TX, USA)
	方法	Evaluation of the inhibitory activity
	细胞系/动物模型	Human NSCLC cell line NCI-H1975
	浓度	100 mM
	处理时间
	实验结果	In addition, the suppression of mTOR phosphorylation decreased the percentage of early apoptotic cells (Figure 6A and 6B) and caspase 3 cleavage (Figure 6C).

	数据来源	Int J Clin Exp Med (2017) . Figure 5. 3-methyladenine (3-MA) (Abmole Bioscience Inc. Houston, TX, USA)
	方法	Evaluation of the inhibitory activity
	细胞系/动物模型	Human NSCLC cell line NCI-H1975
	浓度	100 mM
	处理时间
	实验结果	As a control, 3-MA was used to prevent mTOR phosphorylation. The suppression of mTOR phosphorylation decreased the number of intracellular autophagosomes increased by treatment with wogonin plus icotinib combination (Figure 5B).

	数据来源	Mol Immunol (2017) . Figure 2. 3-methyladenine (Abmole Bioscience, USA)
	方法	IL-37 induces autophagy in SMMC-7721 and Huh-7 cells.
	细胞系/动物模型	SMMC-7721 and Huh-7 cells
	浓度	5 mmol/l
	处理时间
	实验结果	The LC3-II/LC3-I ratio was significantly decreased in IL-37/3-MA-co-treated SMMC-7721 and Huh-7 cells and increased in IL-37/CQ-co-treated SMMC-7721 and Huh-7 cell (Fig. 2E and F). Together, these data further indicate that IL-37 induces autophagy in SMMC-7721 and Huh-7 cells.

实验参考

体外实验*
细胞系	U251 cells
方法	Western blotting was performed to determine the expression levels of ubiquitinated proteins, PDI and Grp78. The expression levels of ubiquitinated PDI and Grp78 were increased following the inhibition of autophagy by treatment with 3-MA
浓度	10 mM
处理时间	12 h

*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	Male Wistar rats
配制	saline
剂量	3.5 mg/kg
给药处理	i.v.

*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	149.15
分子式	C6H7N5
CAS号	5142-23-4
溶解性（25°C）	Water 6 mg/mL warmed
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	6.7047 mL	33.5233 mL	67.0466 mL
5 mM	1.3409 mL	6.7047 mL	13.4093 mL
10 mM	0.6705 mL	3.3523 mL	6.7047 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] Peng Chen, et al. Ecotoxicol Environ Saf. The regulatory role of COX-2 in the interaction between Cr(VI)-induced endoplasmic reticulum stress and autophagy in DF-1 cells

[2] Dae Wook Hwang, et al. Pancreas. Autophagy Induced by CX-4945, a Casein Kinase 2 Inhibitor, Enhances Apoptosis in Pancreatic Cancer Cell Lines

[3] Zhang R, et al. Mol Med Rep. Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells.

[4] Zhu B, et al. Int J Clin Exp Med. 3-methyladenine, an autophagic inhibitor, attenuates therapeutic effects of sirolimus on scopolamine-induced cognitive dysfunction in a rat model.

[5] Hualei Guo, et al. Cardiovasc Drυgs Ther. Resveratrol protects HUVECs from oxidized-LDL induced oxidative damage by autophagy upregulation via the AMPK/SIRT1 pathway

[6] Ying Xie, et al. Mol Med Rep. Protective role of autophagy in AGE-induced early injury of human vascular endothelial cells