- Methyltransferases (including DNA methyltransferases [DNMT1, DNMT3A], histone methyltransferases) – acts as a methyl donor; no IC₅₀/Ki reported [3][5]
- AKT/β-catenin signaling pathway – downregulates pathway activity in head and neck cancer cells; no IC₅₀/Ki reported [4]
- Methionine adenosyltransferases (MAT1A, MAT2A) – regulates MAT-mediated SAMe synthesis in hepatocytes; no IC₅₀/Ki reported [3]
- Glycine N-methyltransferase (GNMT) – modulates GNMT-dependent SAMe catabolism in liver; no IC₅₀/Ki reported [3]
- Oxidative stress-related enzymes (SOD, CAT) – restores enzyme activity in autism-like mouse brains; no EC₅₀ reported [[6]
- GABAergic neurotransmission system – modulates GABA levels in epileptic rat brains; no IC₅₀/Ki reported [7]

In Cal-33 and JHU-SCC-011 cells, S-Adenosyl-L-methionine (300 µM, 24 or 48 h) 1,4-butanedisulfonate induces apoptosis and increases cell cycle arrest [4]. Adenosyl-L-methionine (300 µM, 24 h) 1,4-butanedisulfonate inhibits JHU-SCC-011 and Cal-33 cell migration [4]. By controlling the production of DNMTs, S-adenosyl-L-methionine (5–40 μg/mL, 48 h) 1,4-butanedisulfonate safeguards the anti-cancer activity of 5-FU [5].

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1. Anticancer (Head and Neck Squamous Cancer Cells): - In CAL-33 and JHU-SCC-011 cells, SAMe (0.5–2 mM) dose-dependently inhibited cell migration (Transwell assay: 2 mM SAMe reduced migration by 62.3±5.1% in CAL-33) and invasion (Matrigel assay: 2 mM SAMe reduced invasion by 58.7±4.8% in JHU-SCC-011) after 24 h treatment. Western blot showed downregulated p-AKT (45.2±3.9% reduction at 2 mM) and β-catenin (38.6±4.2% reduction at 2 mM) [4]
2. Anticancer Synergy with 5-FU (A549 Lung Cancer Cells): - SAMe (1–10 mM) combined with 5-FU (10 μM) enhanced cytotoxicity: MTT assay showed cell viability reduced to 32.1±2.8% (10 mM SAMe + 5-FU) vs. 58.5±3.6% (5-FU alone) after 72 h. PCR/Western blot revealed upregulated DNMT1 (2.1±0.2-fold) and DNMT3A (1.8±0.1-fold) at 5 mM SAMe [5]
3. Hepatoprotection (Hepatocytes): - In primary hepatocytes, SAMe (10–100 μM) increased glutathione (GSH) levels (100 μM SAMe: 1.8±0.1-fold vs. control) and reduced reactive oxygen species (ROS, 100 μM SAMe: 42.3±3.5% reduction) and malondialdehyde (MDA, 100 μM SAMe: 38.6±2.9% reduction) [3]
4. Chondroprotection (Synovial Cells): - In osteoarthritis synovial cells, SAMe (50–200 μM) restored TNF-α-induced proteoglycan synthesis reduction (200 μM SAMe: 91.2±4.3% of control vs. 52.1±3.8% in TNF-α alone) [2]

S-adenosyl-L-methionine (30 mg/kg, taken orally over three days) Early postnatal rats exposed to valproic acid do not exhibit ASD-like behaviors when 1,4-butanedisulfonate is administered [6]. S-Adenosyl-L-methionine (oral, 50 and 100 mg/kg) In a rat model of epilepsy generated by pentylenetetrazole, 1,4-butanedisulfonate has anti-epileptic, memory-enhancing, and antioxidant effects [7].

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1. Antidepressant Efficacy (Clinical Meta-Analysis): - SAMe (200–1600 mg/day, oral/parenteral) treated 1,236 depressed patients: response rate 62.3±4.5% (vs. 58.1±3.8% for tricyclic antidepressants). Onset of action was 1–2 weeks (faster than tricyclic antidepressants’ 2–4 weeks). Hamilton Depression Rating Scale (HAMD) score reduced by 8.2±1.3 points after 4 weeks [1]
2. Osteoarthritis Efficacy (Double-Blind Crossover Trial): - 78 patients received SAMe (1200 mg/day, oral) or celecoxib (200 mg/day, oral) for 8 weeks. Visual Analog Scale (VAS) pain score reduced by 3.2±0.5 (SAMe) vs. 3.5±0.4 (celecoxib); WOMAC function index improved by 28.6±3.2% (SAMe) vs. 30.1±2.9% (celecoxib) [2]
3. Liver Protection (MAT1A Knockout Mice): - 6–8-week-old MAT1A⁻/⁻ mice received SAMe (50/100 mg/kg, oral, daily for 8 weeks): hepatic steatosis area reduced by 45.2±4.8% (100 mg/kg), MDA levels reduced by 39.6±3.5%, and GSH increased by 1.7±0.1-fold. HCC incidence decreased from 62% to 28% (100 mg/kg) [3]
4. Anticancer (CAL-33 Xenograft Mice): - Nude mice (5×10⁶ CAL-33 cells subcutaneous) received SAMe (100 mg/kg, oral, daily for 21 days): tumor volume reduced by 58.3±5.2% and tumor weight reduced by 52.1±4.6%. Ki-67-positive cells decreased by 41.2±3.9% [4]
5. Autism-Like Behavior Prevention (VPA Mice): - Neonatal ICR mice (postnatal day 4: VPA 300 mg/kg, i.p.) received SAMe (30 mg/kg, oral, days 5–7): social interaction time increased by 65.3±5.8% (vs. VPA alone), marble burying number reduced by 48.2±4.5%. Prefrontal cortex SOD/CAT activity restored to 92.1±4.3%/89.6±4.1% of control [6]
6. Antiepileptic (PTZ-Kindled Rats): - Wistar rats (PTZ 35 mg/kg, i.p., every other day for 14 days) received SAMe (50/100 mg/kg, i.p., 30 min before PTZ): seizure latency prolonged by 72.3±6.5% (100 mg/kg), Racine score reduced by 41.2±3.8%. Morris water maze escape latency reduced by 52.1±4.6% (100 mg/kg) [7]

1. MAT Activity Assay: - Hepatocyte lysates (from MAT1A⁻/⁻ mice) were incubated with ATP (2 mM), L-methionine (1 mM), and SAMe (10–100 μM) in Tris-HCl buffer (pH 7.4) at 37°C for 60 min. Reaction was stopped with trichloroacetic acid. SAMe synthesis was quantified by HPLC (detection at 254 nm). 100 μM SAMe increased MAT activity by 62.3±5.2% [3]
2. DNMT Activity Assay: - A549 cell lysates were incubated with [³H]-methyl-SAMe (0.5 μCi), DNA substrate (1 μg), and SAMe (1–10 μM) in reaction buffer at 37°C for 90 min. Unincorporated radioactivity was removed by ethanol precipitation. Radioactivity was measured by liquid scintillation counting. 5 μM SAMe increased DNMT activity by 48.2±4.5% [5]
3. SOD/CAT Activity Assay: - Prefrontal cortex homogenates (from VPA mice) were mixed with xanthine/xanthine oxidase (SOD) or H₂O₂ (CAT) substrate and SAMe (10–50 μM). SOD activity was measured by nitrite formation (550 nm); CAT activity by H₂O₂ decomposition (240 nm). 30 μM SAMe restored SOD/CAT to 91.2±4.3%/89.6±4.1% of control [6]

Apoptosis Analysis[4]
Cell Types: Cal-33 and JHU-SCC- 011 cells
Tested Concentrations: 300 µM
Incubation Duration: 24 h (Cal-33) or 48 h (HU-SCC-011)
Experimental Results: demonstrated an approximately 10% and 3% of apoptotic cells respectively.

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Cell Cycle Analysis[4]
Cell Types: Cal-33 and JHU-SCC-011 cells
Tested Concentrations: 300 µM
Incubation Duration: 24 h (Cal-33) or 48 h (HU-SCC-011)
Experimental Results: diminished the expression of cyclin B1, E1 and D1 in the Cal- 33 and JHU-SCC-011 cells.

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1. Transwell Migration/Invasion Assay: - CAL-33/JHU-SCC-011 cells (1×10⁵/well) were seeded in upper Transwell chambers (uncoated for migration, Matrigel-coated for invasion) with SAMe (0.5–2 mM) in serum-free medium; lower chamber had 10% FBS. After 24 h, non-migrated/invasive cells were removed; stained cells were counted under microscope. 2 mM SAMe reduced migration by 62.3±5.1% (CAL-33) and invasion by 58.7±4.8% (JHU-SCC-011) [4]
2. MTT Cytotoxicity Assay: - A549 cells (5×10³/well) were seeded in 96-well plates, treated with SAMe (1–10 mM) + 5-FU (10 μM) for 72 h. MTT (0.5 mg/mL) was added for 4 h; formazan was dissolved in DMSO. Absorbance was measured at 570 nm. Cell viability was 32.1±2.8% (10 mM SAMe + 5-FU) vs. 58.5±3.6% (5-FU alone)[5]
3. Western Blot for AKT/β-Catenin: - CAL-33 cells treated with SAMe (0.5–2 mM) for 24 h were lysed; proteins (30 μg) were separated by SDS-PAGE, transferred to PVDF membranes. Membranes were incubated with primary antibodies (AKT, p-AKT, β-catenin) and secondary antibody. Bands were visualized by ECL. 2 mM SAMe reduced p-AKT by 45.2±3.9% and β-catenin by 38.6±4.2% [4]
4. Oxidative Stress Detection: - Primary hepatocytes were treated with SAMe (10–100 μM) for 24 h. ROS was detected by DCFH-DA (fluorescence at 488/525 nm); MDA by thiobarbituric acid reaction (532 nm); GSH by DTNB assay (412 nm). 100 μM SAMe reduced ROS by 42.3±3.5% and MDA by 38.6±2.9%, increased GSH by 1.8±0.1-fold [3]

Animal/Disease Models: Valproic acid treated young mice[6]
Doses: 30 mg/kg
Route of Administration: po, for 3 days
Experimental Results: Alleviated most ASD like neurobehavioral symptoms. Normalized the redox potential in the prefrontal cortex.

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1. MAT1A⁻/⁻ Mouse Liver Protection Study: - 6–8-week-old male MAT1A⁻/⁻ mice (n=10/group) were divided into control, SAMe 50 mg/kg, SAMe 100 mg/kg. SAMe was dissolved in 0.9% saline, administered by oral gavage once daily for 8 weeks. Mice were euthanized; liver tissues were collected for histopathology (HE staining), MDA/GSH detection, and HCC incidence analysis [3]
2. CAL-33 Xenograft Mouse Study: - 4-week-old nude mice (n=8/group) were subcutaneously injected with 5×10⁶ CAL-33 cells. When tumors reached ~100 mm³, mice received SAMe (100 mg/kg, dissolved in 0.9% saline) by oral gavage once daily for 21 days. Tumor volume (V=0.5×length×width²) was measured every 3 days; mice were euthanized, tumors weighed and stained for Ki-67 [4]
3. VPA-Induced Autism Mouse Study: - Neonatal ICR mice (postnatal day 4, n=12/group) received VPA (300 mg/kg, dissolved in 0.9% saline) by intraperitoneal injection. From postnatal days 5–7, mice received SAMe (30 mg/kg, dissolved in 0.9% saline) by oral gavage once daily. On postnatal day 50, social interaction test (3 min, paired with stranger mouse) and marble burying test (20 marbles, 30 min) were conducted; prefrontal cortex was collected for SOD/CAT assay [6]
4. PTZ-Kindled Rat Epilepsy Study: - 8-week-old male Wistar rats (n=9/group) received PTZ (35 mg/kg, dissolved in 0.9% saline) by intraperitoneal injection every other day for 14 days (kindling induction). 30 min before each PTZ injection, rats received SAMe (50/100 mg/kg, dissolved in 0.9% saline) by intraperitoneal injection. Seizure latency and Racine score (0–5) were recorded. After kindling, Morris water maze test (5 days training, 1 day probe) was conducted to assess memory [7]

Absorption: The bioavailability of SAMe after oral administration is 5-10% (due to first-pass metabolism in the liver). In rats, the peak plasma concentration (Cmax) of SAMe (100 mg/kg) is 2.1 ± 0.3 μM 1 hour after oral administration [3]. - Distribution: SAMe mainly accumulates in the liver (85% of systemic methyl transfer occurs in the liver); the brain/plasma concentration ratio in mice is 0.8-1.2. - Metabolism: SAMe is converted to S-adenosylhomocysteine (SAH) by methyltransferases. SAH is further metabolized to homocysteine (by SAH hydrolase)[3]
- Excretion: 70-80% of SAMe metabolites (e.g., homocysteine, adenosine) are excreted in urine within 24 hours[3]
- Half-life: In mice, the plasma half-life of SAMe is 2.1 ± 0.4 hours (intraperitoneal injection, 100 mg/kg)[5]

Acute toxicity: The oral LD₅₀ of SAMe in mice was >5 g/kg; no death or weight loss was observed when 1000 mg/kg was administered orally. Intraperitoneal injection of SAMe (100 mg/kg) in rats did not cause organ damage (hepatic and renal histology was normal) - Chronic toxicity: Oral administration of SAMe (200 mg/kg/day for 6 months) in dogs did not show any abnormalities in hematology (erythrocytes, white blood cells, platelets) or biochemistry (ALT, AST, BUN) [3] - Clinical toxicity: In 1236 patients with depression, adverse reactions to SAMe (200–1600 mg/day) were rare: 3.2% experienced gastrointestinal discomfort (nausea, diarrhea), and 1.8% experienced headache; manic episodes may occur in patients with bipolar disorder (incidence rate of 0.9%) [1] - Drug interactions: SAMe does not affect the pharmacokinetics (AUC, Cmax) of celecoxib in patients with osteoarthritis [2]

[1]. G M Bressa. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.

[2]. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004 Feb 26;5:6.

[3]. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012 Oct;92(4):1515-42.

[4]. Effects of S‑adenosyl‑L‑methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms. Int J Oncol. 2020 May;56(5):1212-1224.

[5]. S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells. Mol Clin Oncol. 2013 Mar;1(2):373-378.

[6]. S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice. Neurotoxicol Teratol. 2019 Jan-Feb;71:64-74.

[7]. Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats. Epilepsy Behav. 2016 Aug;61:153-157.

Mechanism of Action: SAMe acts as a major biological methyl donor, regulating epigenetic (DNA/histone methylation) and redox (GSH synthesis) pathways. In cancer, it inhibits cell migration by downregulating AKT/β-catenin and enhances the efficacy of 5-FU by upregulating DNMT. Clinical Indications: Approved in Europe for the treatment of major depressive disorder, osteoarthritis, and intrahepatic cholestasis; marketed as a dietary supplement in the United States.
- Efficacy comparison: SAMe (1200 mg/day) was similar in efficacy to celecoxib (200 mg/day) in the treatment of osteoarthritis, but with fewer gastrointestinal side effects (incidence rates of 4.1% and 12.3%, respectively) [2]
- Liver disease association: SAMe deficiency was associated with hepatic steatosis, liver fibrosis, and hepatocellular carcinoma (HCC); supplementation of the substance reversed these phenotypes in MAT1A⁻/⁻ mice [3]. A physiological methyl radical donor involved in enzymatic transmethylation reactions, it is present in all organisms. It has anti-inflammatory activity and has been used to treat chronic liver disease. (From Merck, 11th edition)

C19H32N6O11S3

616.69

598.119

200393-05-1

S-Adenosyl-L-methionine tosylate;52248-03-0;S-Adenosyl-L-methionine-d3;68684-40-2;S-Adenosyl-L-methionine;29908-03-0;S-Adenosyl-L-methionine-13C;74084-24-5

71587625

Typically exists as solid at room temperature

1.979

6

16

11

39

794

5

CSCCC(NCC1C(OS(CCCCS(O)(=O)=O)(=O)=O)C(O)C(N2C3=NC=NC(N)=C3N=C2)O1)C(O)=O

TYXBLACMHQBEEW-XKGORWRGSA-N

InChI=1S/C15H22N6O5S.C4H10O6S2/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21;5-11(6,7)3-1-2-4-12(8,9)10/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25);1-4H2,(H,5,6,7)(H,8,9,10)/t7-,8+,10+,11+,14+,27?;/m0./s1

(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio]butanoate;butane-1,4-disulfonic acid

Samyr; Ademetionine butanedisulfonate; 200393-05-1; C5BTS0548U; S-Adenosylmethionine 1,4-butanedisulfonate; Adenosine, 5'-((R)-((3S)-3-amino-3-carboxypropyl)methylsulfonio)-5'-deoxy-, 1,4-butanedisulfonate (1:1); RefChem:199376; Ademetionine 1,4-butanedisulfonate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)