| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
As an internal standard, the labeled compound has no pharmacological target; it serves as a tracer. However, the unlabeled 6-MP is a purine antimetabolite that targets the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It is converted intracellularly to thioinosine monophosphate (TIMP), which then inhibits de novo purine synthesis. Additionally, TIMP is converted to thioguanine nucleotides (6-TGNs) that incorporate into DNA and RNA, causing chain termination and apoptosis. 6-MP also inhibits Rac1 activation via binding to Vav, leading to T-cell apoptosis (immunosuppression).
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
Not applicable for the labeled compound as a tracer. In vitro, unlabeled 6-MP shows IC50 values of 0.1-1 microM against various leukemia cell lines (e.g., CCRF-CEM, MOLT-4). It induces S-phase cell cycle arrest and activates the mitochondrial apoptosis pathway (caspase-3, Bax upregulation). The labeled version is chemically identical but used only as a mass spec standard; it does not contribute to bioactivity in assays because it is added at trace levels (e.g., 10 ng/mL) that are far below the pharmacological IC50. |
| ln Vivo |
Not applicable for the labeled standard. Unlabeled 6-MP is used clinically in pediatric acute lymphoblastic leukemia (ALL), inflammatory bowel disease (Crohn's, ulcerative colitis), and autoimmune disorders. Its in vivo efficacy correlates with intracellular levels of 6-TGNs. The labeled compound is not administered to humans except as part of bioanalytical studies (microdosing) or in research animals to validate PK methods.
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| Enzyme Assay |
In vitro enzyme (HGPRT) assay: Incubate 50 microg of recombinant human HGPRT with 10 microM 6-MP, 2 mM PRPP (phosphoribosyl pyrophosphate), and varying concentrations of 6-MP (0.01-100 microM) in Tris-HCl buffer, pH 7.4, for 30 min at 37degC. The reaction product, thioinosine monophosphate (TIMP), is quantified by HPLC-UV or LC-MS/MS using 6-Mercaptopurine-13C2,15N as an internal standard. The Km and Vmax are calculated. For receptor binding: 6-MP does not directly bind to a cell surface receptor.
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| Cell Assay |
Cellular metabolism assay: Human hepatocytes (1×10^6 cells/mL) or leukemia cell lines are incubated with 5 microM 6-MP for 0-24 h. The reaction is terminated by adding ice-cold acetonitrile containing 6-Mercaptopurine-13C2,15N (50 ng/mL). Cells are lysed by sonication, centrifuged, and the supernatant is analyzed by LC-MS/MS. Metabolites measured: 6-MP, TIMP, 6-methylmercaptopurine (6-MMP), 6-thiouric acid, and 6-thioguanine nucleotides (6-TGNs). Standard curves are constructed using unlabeled analytes and the labeled internal standard.
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| Animal Protocol |
Animal PK study: Male Sprague-Dawley rats (250-300 g, n=6 per group) are administered unlabeled 6-MP orally (50 mg/kg) or intravenously (10 mg/kg). Blood samples (0.1 mL) are collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Plasma is separated and 50 microL is mixed with 150 microL acetonitrile containing 50 ng/mL of 6-Mercaptopurine-13C2,15N. After centrifugation, the supernatant is analyzed by LC-MS/MS in positive ion mode (MRM transitions: 6-MP: m/z 153→119; labeled: 156→122). PK parameters are computed using WinNonlin. Tissue distribution: liver, kidney, spleen, and small intestine are collected at 2 h post-dose, homogenized, and similarly analyzed.
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| ADME/Pharmacokinetics |
For unlabeled 6-MP: oral bioavailability in rats is ~10-20%, with a peak plasma concentration (Cmax) of ~1-2 microM at 1-2 h post-dose (50 mg/kg). Plasma half-life is 0.5-1 h. Volume of distribution is large (Vd > 1 L/kg) indicating extensive tissue binding. Metabolism is mainly via xanthine oxidase (XO) to 6-thiouric acid (inactive) and via thiopurine methyltransferase (TPMT) to 6-MMP (hepatotoxic). Genetic polymorphisms in TPMT greatly affect PK. The labeled compound follows identical PK and is used to calibrate measurements.
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| Toxicity/Toxicokinetics |
The labeled compound is non-toxic at tracer amounts (micrograms). Unlabeled 6-MP has narrow therapeutic index: common toxicities include myelosuppression (neutropenia, thrombocytopenia), hepatotoxicity (cholestasis, necrosis), and pancreatitis (especially in IBD patients). Nausea, vomiting, and rash are also reported. Rare but severe: secondary malignancies (e.g., hepatosplenic T-cell lymphoma). The labeled standard should be handled with care using cytotoxic drug precautions (gloves, safety cabinet).
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| References |
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| Additional Infomation |
6-Mercaptopurine-13C2,15N is a research-grade internal standard, not for human therapeutic use. It is essential for therapeutic drug monitoring (TDM) in leukemia and IBD patients to optimize dosing (targeting 6-TGN levels between 235-450 pmol/8×10^8 RBCs). It also enables metabolite profiling studies to understand resistance mechanisms (e.g., TPMT deficiency, XO overactivity). No clinical trials are conducted for the labeled compound itself. It is commercially available but as a chemical standard, not a drug product.
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| Molecular Formula |
C5H4N4S
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|---|---|
| Molecular Weight |
152.17705821991
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| Exact Mass |
155.019
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| CAS # |
1190008-04-8
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| Related CAS # |
6-Mercaptopurine;50-44-2
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| PubChem CID |
45039032
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| Appearance |
White to off-white solid powder
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| LogP |
0
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
10
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| Complexity |
190
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC(=S)C2=[13C](N1)N=[13CH][15NH]2
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| InChi Key |
GLVAUDGFNGKCSF-JDKPDMQJSA-N
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| InChi Code |
InChI=1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)/i1+1,4+1,6+1
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| Chemical Name |
3,7-dihydropurine-6-thione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.5712 mL | 32.8558 mL | 65.7117 mL | |
| 5 mM | 1.3142 mL | 6.5712 mL | 13.1423 mL | |
| 10 mM | 0.6571 mL | 3.2856 mL | 6.5712 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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