3-Methyladenine

Names

[ Name ]:
3-Methyladenine

[Synonym ]:
3-Methyl-3H-purin-6-amine
EINECS 225-908-6
methyladenine
N(3)-methyladenine
3-methyl-3H-adenine
3-MA,6-Amino-3-methylpurine
3-methylpurin-6-amine
MFCD00010531
3H-Purin-6-amine, 3-methyl-
6-Amino-3-methylpurine
3-Methyladenine
3-MA

Biological Activity

[Description]:

3-Methyladenine is a PI3K inhibitor. 3-Methyladenine is a widely used inhibitor of autophagy via its inhibitory effect on class III PI3K.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Autophagy >> Mitophagy

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Research Areas >> Cancer

Natural Products >> Alkaloid

[Target]

PtdIns3Kγ:60 μM (IC50, Cell Assay)

Vps34:25 μM (IC50, Cell Assay)

Human Endogenous Metabolite

Autophagy

Mitophagy

[In Vitro]

3-Methyladenine shows slight preference to binds to Vps34 in vitro, with an IC50 of 25 µM for Vps34 as compared with 60 µM for PtdIns3Kγ, and 3-Methyladenine (10 mM) can inhibit all PtdIns3Ks[1]. 3-Methyladenine (3-MA, 5 mM) suppresses autophagy in HeLa cells under both glucose-free conditions and normal conditions. 3-Methyladenine (2.5, 5 or 10 mM) induces caspase-dependent cell death in HeLa cells, and the death occurs independently of the inhibition of autophagy. Moreover, 3-Methyladenine (3-MA, 1 mM) significantly shortens the duration of nocodazole-induced-prometaphase arrest[2].

[In Vivo]

3-Methyladenine (1.5 mg/100 g, i.p.) treatment alleviates sodium taurocholate-induced severe acute pancreatitis (SAP) in rats at both 12 and 24 h. 3-Methyladenine inhibits autophagy of pancreatic acinar cells in sodium taurocholate-tnduced SAP. 3-Methyladenine also shows inhibitory effects on PI3K/Akt signaling pathway and NF-κB signaling pathway in sodium taurocholate-tnduced SAP[3].

[Cell Assay]

Cell viability is determined by a trypan blue exclusion assay. Cells are cultured in the medium with 3-Methyladenine. Both adherent and floating cells are collected and suspended in phosphate buffered saline (PBS, pH 7.4) at a final density of 1-2×106/mL. An equal volume of 0.4% trypan blue solution (w/v, in PBS) is added to the cell suspension and mixed thoroughly. After incubation at room temperature for 3 min, cell counting is performed using a hemacytometer.

[Animal admin]

All rats are fasted for 12 h with free access to water prior to operation. After anesthesia by intraperitoneal (i.p.) injection of 2% sodium pentobarbital (0.25 mL/100 g), they are laid and fixed on the table, routinely shaven, disinfected, and draped. The rat SAP model is induced by 0.1 mL/min speed uniformly retrograde infusion of a freshly prepared 3.5% sodium taurocholate solution (0.1 mL/100 g) into the biliopancreatic duct after laparotomy. Equivalent volume of normal saline solution is substituted for 3.5% sodium taurocholate solution in the sham-operation (SO) control group. The incision is closed with a continuous 3-0-silk suture, and 2 mL/100 g of saline is injected into the back subcutaneously to compensate for the fluid loss. 180 rats are randomly divided into four groups: (1) Acanthopanax treatment group (Aca group, n = 45) where the rats are injected with 0.2% Acanthopanax injection at a dose of 3.5 mg/100 g 3 h after successful modeling via the vena caudalis once, knowing that this dosage is effective; (2) 3-Methyladenine treatment group (3-methyladenine group, n = 45) where the rats are injected with 100 nmol/μL 3-methyladenine solution at a dose of 1.5 mg/100 g 3 h after successful modeling via the intraperitoneal route once, knowing that this dosage is effective; (3) SAP model group (SAP group, n = 45) where these rats receive an equivalent volume of the normal saline instead of Acanthopanax injection 3 h after successful modeling via the vena caudalis once; (4) SO group (control, n = 45) where these rats receive an equivalent volume of the normal saline instead of Acanthopanax injection 3 h after successful sham-operation via the vena caudalis once. The 45 animals in each of the four groups are equally randomized into 3, 12, and 24 h subgroups for postoperative observations[3].

[References]

[1]. Miller S, et al. Finding a fitting shoe for Cinderella: searching for an autophagy inhibitor. Autophagy. 2010 Aug;6(6):805-807.

[2]. Hou H, et al. Inhibitors of phosphatidylinositol 3'-kinases promote mitotic cell death in HeLa cells. PLoS One. 2012;7(4):e35665.

[3]. Wang X, et al. Acanthopanax versus 3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats. Mediators Inflamm. 2016;2016:8369704.

[4]. Meng Li, et al. Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice. J Immunol Res. 7 August 2018.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
240.1±50.0 °C at 760 mmHg

[ Melting Point ]:
-300ºC (dec.)(lit.)

[ Molecular Formula ]:
C₆H₇N₅

[ Molecular Weight ]:
149.153

[ Flash Point ]:
99.0±30.1 °C

[ Exact Mass ]:
149.070145

[ PSA ]:
69.62000

[ LogP ]:
-2.36

[ Appearance of Characters ]:
Powder | White

[ Vapour Pressure ]:
0.0±0.5 mmHg at 25°C

[ Index of Refraction ]:
1.807

[ Storage condition ]:
Store at +4°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AU6520000

CHEMICAL NAME :: Adenine, 3-methyl-

CAS REGISTRY NUMBER :: 5142-23-4

BEILSTEIN REFERENCE NO. :: 0146087

LAST UPDATED :: 199712

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C6-H7-N5

MOLECULAR WEIGHT :: 149.18

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 280 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 46(5),104,1983

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

[ Safety Phrases ]:
24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
AU6520000

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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