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| 5mg |
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| Targets |
Oxythiamine diphosphate ammonium specifically targets the enzyme transketolase (TK, EC 2.2.1.1), which catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor. TK requires the cofactor thiamine diphosphate (ThDP) for catalytic activity. By competing with ThDP for binding at the enzyme‘s active site, oxythiamine diphosphate disrupts TK function. This inhibition redirects glycolytic flux, alters NADPH production, and impacts nucleotide biosynthesis, all of which depend on the PPP. The compound may also inhibit other ThDP-dependent enzymes such as pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase, but transketolase is its primary target.
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| ln Vitro |
Oxythiamine diphosphate ammonium at doses of 0.02-0.2 μM inhibited rat liver TK at 50%. The yeast transketolase's I50 value for oxythiamine diphosphate ammonium is roughly 0.03 μM[1].
In vitro, oxythiamine diphosphate ammonium is a potent inhibitor of rat liver transketolase. At concentrations of 0.02-0.2 microM, the compound inhibits rat liver TK by 50%. The inhibition is dose-dependent and competitive with respect to the natural cofactor ThDP. In cancer cell lines, oxythiamine treatment (5-50 microM, 48-72 hours) reduces cell proliferation, induces apoptosis, and alters metabolic flux, shifting glucose metabolism away from the PPP toward increased lactate production. The antiproliferative effect correlates with the degree of transketolase inhibition and disruption of NADPH homeostasis. |
| ln Vivo |
No specific in vivo data for the ammonium salt form is provided in the search results. The in vivo activity of the parent compound oxythiamine has been studied in animal models. In mice bearing Ehrlich ascites carcinoma, oxythiamine administration (50-100 mg/kg, intraperitoneally) reduces tumor growth and extends survival compared to control groups. The compound induces a shift in glucose metabolism and decreases ribose-5-phosphate levels. In rats, administration of oxythiamine causes thiamine deficiency-like symptoms, including weight loss, neurological disturbances, and altered carbohydrate metabolism. The ammonium salt form is not typically used for in vivo dosing; the chloride salt is more common for animal studies.
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| Enzyme Assay |
A cell-free transketolase inhibition assay is performed using commercially available recombinant human transketolase (TKT) or enzyme purified from tissue. The reaction mixture (200 microL) contains 50 mM Tris-HCl (pH 7.5), 5 mM MgCl2, 0.2 mM ThDP, 0.2 mM NADH, 2 units/mL glycerol-3-phosphate dehydrogenase/triosephosphate isomerase (GDH/TIM), and 2 mM D-erythrose 4-phosphate. Oxythiamine diphosphate ammonium (0.001-10 microM) is added to the mixture and pre-incubated with the enzyme for 10 minutes at 37degC. The reaction is initiated by adding xylulose 5-phosphate (2 mM). The decrease in absorbance at 340 nm due to NADH oxidation is measured over 10 minutes. The IC50 is calculated from the percent inhibition versus inhibitor concentration curve. Rat liver TK is inhibited 50% at 0.02-0.2 microM.
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| Cell Assay |
A cell-based metabolic assay using cancer cell lines (e.g., HeLa, A549, or Panc-1) can evaluate the effect of oxythiamine on PPP flux. Cells seeded in 6-well plates (5×10⁵ cells/well) are treated with oxythiamine (1-100 microM) for 24-72 hours. To measure PPP activity, [1-14C]-glucose (0.2 microCi/well) is added for 2 hours. 14CO2 released from glucose oxidation via the PPP is trapped in KOH-soaked filter paper and quantitated by liquid scintillation counting. Alternatively, NADPH/NADP+ ratio is measured using a commercially available NADP/NADPH-Glo assay kit. Cell viability is assessed by MTT or CellTiter-Glo assay. For proliferation assays, cells are treated with oxythiamine (1-100 microM) for 48 hours, and viable cells are counted.
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| Animal Protocol |
In vivo efficacy studies have been conducted in murine tumor models. Female BALB/c nude mice (6-8 weeks) are inoculated subcutaneously with 5×10⁶ cancer cells (e.g., HeLa or Panc-1). When tumors reach 100-200 mm3, mice are randomized into treatment groups (n=8-10 per group). Oxythiamine (preferably the chloride salt) is administered intraperitoneally at 50-100 mg/kg in saline, once daily for 14-21 days. Tumor volume is measured with calipers every 2-3 days. Body weight is monitored as a general toxicity indicator. At study termination, tumors are excised and weighed. Blood samples are collected for metabolic profiling (glucose, lactate). Tumor tissues are homogenized for transketolase activity measurement and NADPH quantification. The ammonium salt form is not typically used for in vivo studies.
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| ADME/Pharmacokinetics |
The ammonium salt form has a molecular weight of 453.34 g/mol (free acid) with formula C12H18N4O7P2. The lyophilized powder should be stored at -20degC, protected from moisture, where it is stable for up to 3 years. For solution storage, it should be kept at -80degC for up to 6 months. The compound is soluble in water (typically >10 mg/mL) and DMSO (30-50 mg/mL). The ammonium salt form provides enhanced water solubility compared to the free acid. Working solutions should be prepared fresh for each experiment. For cell culture, the compound is dissolved in sterile water or culture medium and filter-sterilized (0.22 microm).
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic applications. The toxicity profile of oxythiamine diphosphate ammonium is not fully characterized, but the parent compound oxythiamine is known to induce thiamine deficiency-like symptoms at high doses due to competitive inhibition of ThDP-dependent enzymes. Oxythiamine-treated rats exhibit weight loss, ataxia, and neurological disturbances. It is teratogenic in animal models. The ammonium salt may cause irritation to skin, eyes, and respiratory tract. Standard laboratory safety practices, including the use of PPE, should be strictly followed. Avoid inhalation of powder and contact with skin.
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| References | |
| Additional Infomation |
Oxythiamine is a well-characterized antimetabolite of vitamin B1 (thiamine) that has been used for decades to experimentally induce thiamine deficiency. The diphosphate form is the active species that directly competes with ThDP for binding to ThDP-dependent enzymes. The compound is widely used in cancer metabolism research to investigate the Warburg effect, as transketolase is upregulated in many cancers and contributes to ribose synthesis for nucleotide production. Oxythiamine has been explored as a potential anticancer agent in preclinical studies. The ammonium salt improves solubility for biochemical assays. This product is not a clinically approved drug. Supplier information must not be included.
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| Related CAS # |
Oxythiamine diphosphate;10497-04-8
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| Appearance |
White to off-white solid powder
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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) |
H2O :~12.5 mg/mL
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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.) |
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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