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ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Urinary excretion of administration p-toluenesulfonamide in rats was approx 80% with half of original compound being oxidized to p-sulfamoylbenzoic acid. More than 90% of /the p-sulfamoylbenzoic acid metabolite/ was excreted unchanged, but urine to feces ratios varied considerably among individual animals. After oral administration of (14)C-labeled compound to rats the label was rapidly eliminated largely in urine (66-89% of dose), with little in feces (2-8% of dose). (14)C in feces was 4-sulfamoylbenzoic acid, which probably originated in tissues. Metabolism / Metabolites /The purpose of this study was/ to study the in vivo and in vitro metabolism and the effect of para-toluene-sulfonamide (PTS) on cytochrome P450 enzymes (CYP450). Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66+/-0.17 and 0.60+/-0.12 nmol/mg. The K(m) and V(max) were 92.2 umol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A. Aim of this study was to investigate liver metabolism of with regard to para toluene-sulfonamide (PTS), CYP isoforms, P-glycoprotein (P-gp), and drug interactions. Known substrates, inducers and inhibitors of CYP and inhibitor of P-gp were employed and metabolites were determined with HPLC. Male Wistar rats were pretreated with ip phenobarbital (PB), ketoconazole (Ket), or verapamil (Ver) for 3 days and in situ liver perfusion of PTS was conducted in a recirculation system. Rats were also pretreated with ip PTS (33 mg/kg/day or PTS 99 mg/kg/day) for 4 days before liver perfusions with dextromethorphan (Dex) and phenacetin (Phe) preparations were conducted. Microsome incubation was used to investigate PTS effect on five CYP isoforms and PTS-drug interactions probability with phyllotoxin and 5-fluorouracil (5-FU) in vitro. PTS at 60 min perfusates had areas of 61.4% and 133.6% of the blank control in PB group and Ket group, respectively. The result that PTS metabolism was enhanced by PB and inhibited by Ket treatments suggested liver CYP was attributed to PTS metabolism. PTS mg/kg/day pretreatment slowed down the metabolism of Dex and Phe while in vitro incubations did not show a PTS (0-160 umol/L) effect on CYP activities. PTS metabolite formation when co-incubated with phyllotoxin was 50.7% of the negative control. The potent inhibitory ability of phyllotoxin to PTS requires further clinical investigation regarding in concomitant administration. Fifteen adult rainbow trout were exposed to water solution of (14)C-tosylchloramide sodium (purity 93.7%, specific activity 1.2 ugCi/uM) at a concentration of 20 mg/L (twice the proposed treatment concentration) for a period of 1 hour and then transferred to fresh water. The temperature of the well water was 11 to 13 °C. ... tosylchloramide sodium was rapidly reduced to the primary metabolite para-toluenesulfonamide, but the levels were not quantified. ...50% of admin ortho- and para-toluenesulfonamides excreted in urine had been metabolized to ortho- and para-sulfamoylbenzoic acids, respectively. For more Metabolism/Metabolites (Complete) data for p-Toluenesulfonamide (6 total), please visit the HSDB record page. Biological Half-Life Fingerlings and juvenile trout were exposed to 20 mg/L (twice the therapeutic concentration) of ring UL-14C-tosylchloramide sodium (purity 93.7%, specific activity 1.2 uCi/uM) for up to 1 hr and then transferred to fresh water for recovery to assess tissue accumulation and distribution of resulting residues. The temperature of the well water was 11.6 to 12.2 °C. The estimated half-life of para-toluenesulfonamide equivalents in fingerlings was 27.3 hours whereas determined by HPLC the half-life of para-toluenesulfonamide residues in whole-body homogenates was 36.3 hours. The estimated half-life of residues in juvenile fish was 32.6 hours, based on radiometric data, while determined by HPLC the half-life for para-toluenesulfonamide residues in whole body samples was 40.3 hours. |
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Toxicity/Toxicokinetics |
Toxicity Summary
IDENTIFICATION AND USE: p-Toluenesulfonamide is a solid. It is used in organic synthesis, in plasticizers and resins, and as a fungicide and mildewicide in paints and coatings. It has been used as experimental therapy. HUMAN STUDIES: It is known as a common contact allergen. ANIMAL STUDIES: No treatment-related effects were observed in a 90 day feeding study on dogs exposed to doses up to 3000 mg/kg feed of a mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%), equivalent to 75 mg/kg bw/day. In a 90 day feeding study, rats were exposed to diets containing 0, 300, 1000 or 3000 mg/kg feed of mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%), equivalent to approximately 15, 50 or 150 mg/kg bw/day. A slight reduction of weight gain and food consumption was present at 3000 mg/kg feed as the only treatment-related effects. Pregnant rats were treated by gavage on gestational days 6-15 with 0, 50, 250, or 500 mg/kg bw of a mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%). At 250 and 500 mg/kg bw maternal weight gain was significantly reduced during the treatment period. At the same dose levels, postimplantation loss demonstrated a dose-related increase and fetal weight was reduced. No teratogenic effect was observed. p-Toluenesulfonamide was studied for mutagenic potential with Salmonella typhimurium/microsome test, basic-test in Drosophila melanogaster, and micronucleus test in mice. No test revealed mutagenic activity. Non-Human Toxicity Values LD50 Rat oral 2400 mg/kg bw /Mixture of ortho-toluenesulfonamide (41%) and para-toluenesulfonamide (51%)/ LD50 Rat oral 2330 mg/kg bw LD50 Rat oral >2000 mg/kg LD50 Mouse oral 400 mg/kg LD50 Mouse ip 250 mg/kg |
Additional Infomation |
Toluene-4-sulfonamide is a sulfonamide that is benzenesulfonamide bearing a methyl group at position 4.
Para-toluenesulfonamide is a low-molecular-weight organic compound with potential antineoplastic activity. Upon intra-tumoral injection, para-toluenesulfonamide increases lysosomal membrane permeabilization (LMP) and the release of cathepsin B. Cytosolic cathepsin B released from lysosomes cleaves and activates proapoptotic B-cell lymphoma 2 (Bcl-2) family member BH3 interacting-domain death agonist (Bid) and poly [ADP-ribose] polymerase 1 (PARP-1), which may induce tumor cell death. Therapeutic Uses /CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Para-toluenesulfonamide is included in the database. /EXPL THER/ Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). /The purpose of this study was/ to determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6.9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO. /EXPL THER/ /The purpose was/ to study the effect of percutaneous para-toluenesulfonamide (PTS) injection on transplanted hepatocarcinoma in nude mice. Sixty nude mice with subcutaneous transplanted hepatocarcinoma were randomized into 6 groups, namely PTS, chemotherapy, radiotherapy, PTS+chemotherapy, PTS+radiotherapy and control groups. PTS were injected into the tumor in the nude mouse models as indicated, and the tumor growth rate and survival time of the mice were recorded. All the treatments resulted in effective arrest of the tumor growth, but the effects of PTS+chemotherapy and PTS+radiotherapy were more obvious. No significant difference in the survival time of the mice were noted between the groups. PTS+chemotherapy and PTS+radiotherapy are safe and reliable, and produces better effects than either radiotherapy or chemotherapy alone. /EXPL THER/ Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liquid chromatography showed that PTS selectively accumulated in Tca-8113 cells with a relatively low concentration in normal fibroblasts. Next, the effects of PTS on cell viability, invasion, and cell death were determined. PTS significantly inhibited Tca-8113 cells' viability and invasive ability with increased cancer cell death. Flow cytometric analysis and the lactate dehydrogenase release assay showed that PTS induced cancer cell death by activating apoptosis and necrosis simultaneously. Morphological changes, such as cellular shrinkage, nuclear condensation as well as formation of apoptotic body and secondary lysosomes, were observed, indicating that PTS might induce cell death through disturbing lysosomal stability. Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and induce the release of mitochondrial cytochrome c. Therefore, our findings provide a novel insight into the use of PTS in cancer therapy. /EXPL THER/ Hepatocellular carcinoma (HCC) is difficult to eradicate due to its resilient nature. Portal vein is often involved in tumors of large size, which exclude the patient from surgical resection and local ablative therapy, such as percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) because they were considered neither effective nor safe. Currently, there is almost no effective treatment for HCC of such condition. As a unique antitumor agent in form of lipophilic fluid for local injection, para-toluenesulfonamide (PTS) produces mild side effects while necrotizing the tumor tissues quickly and efficiently. Being largely different from both PEI and RFA therapies, PTS can disseminate itself in tumors more easily than other caustic agents, such as alcohol. So PTS may offer additional benefit to HCCs with vascular involvement. We herein describe a 70-year-old HCC patient who was treated with the combination of PTS injection and transcatheter arterial chemoembolization, resulting in a significantly improved clinical prognosis. |
Molecular Formula |
C7H9NO2S
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Molecular Weight |
171.22
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Exact Mass |
171.035
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CAS # |
70-55-3
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Related CAS # |
4-Tolyl-sulfonamide-d4;1219795-34-2
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PubChem CID |
6269
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Appearance |
Monoclinic plates (w+2)
White leaflets |
Density |
1.3±0.1 g/cm3
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Boiling Point |
322.2±35.0 °C at 760 mmHg
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Melting Point |
134-137 °C(lit.)
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Flash Point |
148.6±25.9 °C
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Vapour Pressure |
0.0±0.7 mmHg at 25°C
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Index of Refraction |
1.564
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LogP |
0.79
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
3
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Rotatable Bond Count |
1
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Heavy Atom Count |
11
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Complexity |
209
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Defined Atom Stereocenter Count |
0
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SMILES |
S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(N([H])[H])(=O)=O
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InChi Key |
LMYRWZFENFIFIT-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C7H9NO2S/c1-6-2-4-7(5-3-6)11(8,9)10/h2-5H,1H3,(H2,8,9,10)
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Chemical Name |
4-methylbenzenesulfonamide
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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 |
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 | 5.8404 mL | 29.2022 mL | 58.4044 mL | |
5 mM | 1.1681 mL | 5.8404 mL | 11.6809 mL | |
10 mM | 0.5840 mL | 2.9202 mL | 5.8404 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.