3-Methyladenine
3-Methyladenine is an inhibitor of class III phosphoinositide 3-kinase (PI3K) [1].
3-Methyladenine is widely used as an autophagy inhibitor through inhibiting class III PI3K without significantly affecting protein synthesis or ATP levels. 3-Methyladenine also inhibits class I PI3K. It is found that 3-Methyladenine has different effects on class I and class III PI3K. It blocks class I PI3K persistently while inhibits class III PI3K transiently. As an inhibitor of autophagy, 3-Methyladenine is usually used to study the role of autophagy. In addition, 3-Methyladenine is also found to have anti-cancer efficacy. It induces cell death of tumor under nutrient-starved conditions. In HT1080 cells, 3-Methyladenine significantly inhibits cell migration through reducing membrane ruffle and lamellipodia formation in normal culture condition. It also inhibits the invasion of HT1080 cells [1, 2].
References:
[1] Wu Y T, Tan H L, Shui G, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. Journal of Biological Chemistry, 2010, 285(14): 10850-10861.
[2] Ito S, Koshikawa N, Mochizuki S, et al. 3-Methyladenine suppresses cell migration and invasion of HT1080 fibrosarcoma cells through inhibiting phosphoinositide 3-kinases independently of autophagy inhibition. International journal of oncology, 2007, 31(2): 261-268.
- 1. Tianyao Liu, Xinyan Xu, et al. "ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape." Cell Death Dis. 2023 Dec 7;14(12):800. PMID: 38062004
- 2. Zhang-Li Yuan, Yan-Zi Mo, et al. "Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury." Cell Commun Signal. 2023 Aug 14;21(1):204. PMID: 37580749
- 3. Zhitao Jiang, Liyuan Gao, et al. "Sarmentosin Induces Autophagy-dependent Apoptosis via Activation of Nrf2 in Hepatocellular Carcinoma." J Clin Transl Hepatol. 2023 Aug 28;11(4):863-876. PMID: 37408810
- 4. Liu B, Yao X, et al. "LINC01278 Induces Autophagy to Inhibit Tumour Progression by Suppressing the mTOR Signalling Pathway." Oxid Med Cell Longev 2023;2023. PMID: 36713034
- 5. Liu B, Yao X, et al. "PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation." Cell Death Dis 2023 Jan 23;14(1). PMID: 36690663
- 6. Yang CZ, Wang SH, et al. "Neuroprotective effect of astragalin via activating PI3K/Akt-mTOR-mediated autophagy on APP/PS1 mice." Cell Death Discov 2023 Jan 21;9(1). PMID: 36681681
- 7. Jingjing Sun, Ziming Wang, et al. "The role and mechanism of LARP7 in regulating the STING-dependent autophagy-lysosomal negative feedback loop in diabetic cardiomyopathy." Research Square. 07 Sep, 2023.
- 8. Tingting Wei, Jiajie Cheng, et al. "Anthocyanins from Lycium ruthenicum Murray inhibit HCC tumor angiogenesis and promote autophagic apoptosis through AMPK/PI3K/AKT/mTOR pathway." Research Square. 07 Sep, 2023.
- 9. Dejuan Sun, Yueying Yang, et al. "Identification of ADP-ribosylation factor 6 as the cellular target of withangulatin A against TNBC cells by ferroptosis." Research Square. October 14th, 2022.
- 10. Yuanhui Zhu, Xi Wang, et al. "Targeting Aβ and p-Tau Clearance in Methamphetamine-Induced Alzheimer's Disease-Like Pathology: Roles of Syntaxin 17 in Autophagic Degradation in Primary Hippocampal Neurons." Oxid Med Cell Longev. 2022 May 18;2022:3344569. PMID: 35633882
- 11. Shuyi Chen, Yabiao Gao, et al. "Anti-cancer Drug Anlotinib Promotes Autophagy and Apoptosis in Breast Cancer." Front Biosci (Landmark Ed). 2022 Apr 7;27(4):125. PMID: 35468684
- 12. Yuan-Yuan Gao, Juan Li, et al. "Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells." Int J Ophthalmol. 2022 Jan 18;15(1):23-30. PMID: 35047352
- 13. Jia-Nan Yan, Hai-Ying Zhang, et al. "Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson's disease." Neural Regen Res. 2022 Jun;17(6):1357-1363. PMID: 34782582
- 14. Du Yu, Yundi Zhao, et al. "C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein." Virol Sin. 2021 Dec;36(6):1443-1455. PMID: 34309824
- 15. Chenghao Li, Jiawei Li, et al. "Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment." J Agric Food Chem. 2021 Jul 28;69(29):8130-8143. PMID: 34269571
- 16. Renjie Dou, Jinjun Qian, et al. "Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma." Cell Death Dis. 2021 Feb 24;12(2):206. PMID: 33627630
- 17. Xiaoli Liu, Yan Gu, et al. "Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation." Apoptosis. 2021 Apr;26(3-4):195-208. PMID: 33550458
- 18. Shichao Lv, Peng Yuan, et al. "QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy." J Cell Mol Med 2020 Sep 2. PMID: 32881330
- 19. Baicun Li, Jie Yao, et al. "Design, synthesis, and biological evaluation of 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole-2-carbohydrazide derivatives as novel Nur77 modulators." Eur J Med Chem. 2020 Oct 15;204:112608. PMID: 32717483
- 20. Shuyi Chen, Ping Zhu, et al. "Anlotinib Inhibits the Growth of Breast Cancer Cells by Promoting Autophagy and Apoptosis via the Akt/GSK-3α Signalling Pathway." Research Square. October 9th, 2020.
- 21. HAIDONG SUN, HUAJIE ZONG, et al. " 2‑Hydroxypropyl‑β‑cyclodextrin blocks autophagy flux and triggers caspase‑8‑mediated apoptotic cascades in HepG2 cells." Mol Med Rep. 2020 Sep;22(3):1901-1909. PMID: 32705246
- 22. Meng XL, Fu P, et al. "Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats." Neurosci Bull. 2020;10.1007/s12264-020-00502-w. PMID: 32346844
- 23. Zhao F, Wang J, et al. "Neuroprotection by Walnut-derived Peptides through Autophagy Promotion via Akt/mTOR Signaling Pathway against Oxidative Stress in PC12 Cells." J Agric Food Chem. 2020;10.1021/acs.jafc.9b08252. PMID: 32090563
- 24. Zhang H, He Y, et al."miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia." Redox Biol. 2020 Jan;29:101402. PMID: 31926626
- 25. Zhou H, Du R, et al. "Cannabinoid receptor 2 promotes the intracellular degradation of HMGB1 via the autophagy-lysosome pathway in macrophage." Int Immunopharmacol. 2020;78:106007. PMID: 31806570
- 26. Chen Y, Zhu E, et al. "Important roles of C-terminal residues in degradation of capsid protein of classical swine fever virus." Virol J. 2019 Nov 6;16(1):127. PMID: 31694654
- 27. Ye J, Xue M, et al. "Diosbulbin B-Induced Mitochondria-Dependent Apoptosis in L-02 Hepatocytes is Regulated by Reactive Oxygen Species-Mediated Autophagy." Front Pharmacol. 2019 Jun 19;10:676. PMID: 31275148
- 28. Tang RH, Qi RQ, et al. "Interleukin-4 affects microglial autophagic flux." Neural Regen Res. 2019 Sep;14(9):1594-1602. PMID: 31089059
- 29. Sarah Needs. "The Biochemical Basis of Congenital Disorders of Glycosylation." The Open University. 2019.
- 30. Gierisch ME, Pfistner F, et al. "Proteasomal Degradation of the EWS-FLI1 Fusion Protein Is Regulated by a Single Lysine Residue." J Biol Chem. 2016 Dec 23;291(52):26922-26933. PMID: 27875302
- 31. Xue H, Yuan G, Guo X, et al. "A Novel Tumor-promoting Mechanism of IL6 and the Therapeutic Efficacy of Tocilizumab: Hypoxia-induced IL6 Is a Potent Autophagy Initiator in Glioblastoma via the p-STAT3-MIR155-3p-CREBRF Pathway[J]." Autophagy, 10 May 2016.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 149.15 |
Cas No. | 5142-23-4 |
Formula | C6H7N5 |
Synonyms | 3-MA |
Solubility | ≥5 mg/mL in H2O; ≥7.45 mg/mL in DMSO; ≥8.97 mg/mL in EtOH |
Chemical Name | 3-methylpurin-6-amine |
SDF | Download SDF |
Canonical SMILES | CN1C=NC(=C2C1=NC=N2)N |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Cell experiment [1]: | |
Cell lines |
HT1080 cells |
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
Reacting condition |
5 or 10 mM; 10 hrs |
Applications |
3-Methyladenine (3-MA) (5 ~ 10 mM) strongly inhibited HT1080 cell migration. In addition, 10 mM 3-MA showed a stronger effect on the suppression of HT1080 cell migration than both 100 nM WMN and 25 μM LY294002. |
References: [1]. Ito S, Koshikawa N, Mochizuki S, et al. 3-Methyladenine suppresses cell migration and invasion of HT1080 fibrosarcoma cells through inhibiting phosphoinositide 3-kinases independently of autophagy inhibition. International journal of oncology, 2007, 31(2): 261-268. |
Description | 3-Methyladenine is a selective inhibitor of PI3K with an IC50 values of 25 μM and 60 μM for Vps34 and PI3Kγ, respectively. | |||||
Targets | Vps34 | PI3Kγ | ||||
IC50 | 25 μM | 60 μM |
Quality Control & MSDS
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Chemical structure

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