| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Hepsulfam acts as an alkylating agent that forms covalent cross-links with DNA. It alkylates nucleophilic centers in DNA, primarily at the N7 position of guanine residues. This leads to the formation of DNA-DNA and DNA-protein cross-links, resulting in depurination, base miscoding, strand scission, and ultimately, cytotoxicity. By blocking DNA replication and transcription, it inhibits tumor cell proliferation.
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| ln Vitro |
Hepsulfam was effective against 8 out of 37 tumors (22%), when used at a concentration of 1.0 μg/mL in clonogenic tests. Human bone marrow cells from healthy donors are significantly hazardous to hepsulfam in vitro (CFU-GM). Hepsulfam has been found to be extremely active in vitro isotoxic concentration assessments, particularly in non-small cell lung cancer [1]. Compared to its structural homologue busulfan, hepsulfam is more hazardous to L1210 leukemia cells. Hepsulfam, but not busulfan, caused DNA interstrand cross-links in L1210 murine leukemia cells, which is consistent with variations in toxicity. When it came to two human leukemia cell lines (111-60 and K562) and two human colon cancer cell lines (HT-29 and BE), hepsulfam was more cytotoxic than busulfan. Hepsulfam produced more DNA interstrand cross-links than busulfan, just as in 11210 cells. When the drug exposure duration was extended to 12 hours and the concentration was lowered tenfold, hepsulfam was likewise more cytotoxic against human leukemia cell lines [2].
Hepsulfam demonstrates potent in vitro anticancer activity. It shows excellent antileukemic activity with a median IC50 of 0.91 µg/mL across a panel of different tumors. As a bifunctional alkylating agent, it effectively induces DNA damage, which is the basis of its cytotoxic effects on cancer cells. Its activity is similar to that of busulfan but with a potentially broader spectrum of activity. |
| ln Vivo |
In gastric cancer models and large cell lung cancer xenografts, hepsulfam has outstanding in vivo activity. Hepsulfam's preclinical activity raises the possibility that this substance could be used to treat solid cancers in people. For further clinical application, hepsulfam's higher bone marrow toxicity in comparison to busulfan may be crucial [1].
Hepsulfam has been evaluated in clinical trials for its antitumor activity. It was designed to improve upon the efficacy of busulfan for cancer treatment. As an alkylating agent, it is expected to have systemic antitumor effects. However, specific in vivo efficacy data is limited in the provided sources. |
| Enzyme Assay |
The primary in vitro assay for Hepsulfam is a cell viability assay using a panel of tumor cell lines. Cells are treated with varying concentrations of the compound, and cell viability is measured after a defined period. The IC50 value is determined from the dose-response curve. The formation of DNA cross-links can also be measured using techniques like the alkaline comet assay or HPLC.
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| Cell Assay |
In vitro cellular experiments for Hepsulfam involve treating cancer cell lines with the compound and measuring its effects on cell proliferation and DNA damage. DNA damage can be assessed by measuring the formation of γ-H2AX foci or by using the comet assay. Cell cycle analysis can be performed by flow cytometry to assess the effects on cell cycle progression.
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| Animal Protocol |
In vivo efficacy of Hepsulfam has been evaluated in clinical trials. In animal models, it would be administered to tumor-bearing mice, and its effects on tumor growth and survival would be assessed. Its pharmacokinetic properties and safety profile would also be characterized.
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| ADME/Pharmacokinetics |
Hepsulfam has a molecular weight of 290.4 g/mol and a molecular formula of C7H18N2O6S2. Its IUPAC name is 7-sulfamoyloxyheptyl sulfamate. It is also known as 1,7-Heptanediol disulfamate. The compound is a white to off-white powder.
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| Toxicity/Toxicokinetics |
Hepsulfam is an anticancer agent that has been evaluated in clinical trials. Its toxicological profile is characteristic of alkylating agents, which can cause myelosuppression, nausea, vomiting, and other side effects. Its safety would need to be carefully managed in a clinical setting. It is a research compound that is not intended for human use outside of clinical trials.
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| References | |
| Additional Infomation |
Heppanamide is a disulfonamide ester with a structure similar to busulfan, belonging to the alkyl sulfonate class of alkylating agents. Heppanamide forms covalent bonds with the nucleophilic center of DNA, leading to depurination, base mismatch, strand breaks, DNA-DNA and DNA-protein crosslinks, and cytotoxicity. (NCI04)
Hepsulfam (NCI 329680) is a bisulfamic ester and a bifunctional alkylating agent structurally similar to busulfan. It was designed to improve upon busulfan's antitumor efficacy and has shown excellent antileukemic activity. It acts by forming covalent cross-links with DNA, thereby inhibiting tumor cell proliferation. It has been evaluated in clinical trials for cancer treatment. |
| Molecular Formula |
C7H18N2O6S2
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|---|---|
| Molecular Weight |
290.35762
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| Exact Mass |
290.061
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| CAS # |
96892-57-8
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| PubChem CID |
100606
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| Appearance |
White to off-white solid powder
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| Density |
1.407g/cm3
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| Boiling Point |
478.2ºC at 760 mmHg
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| Flash Point |
243ºC
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| Index of Refraction |
1.521
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| LogP |
2.939
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
17
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| Complexity |
342
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GOJJWDOZNKBUSR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H18N2O6S2/c8-16(10,11)14-6-4-2-1-3-5-7-15-17(9,12)13/h1-7H2,(H2,8,10,11)(H2,9,12,13)
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| Chemical Name |
7-sulfamoyloxyheptyl sulfamate
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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) |
DMSO : ~100 mg/mL (~344.40 mM)
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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 | 3.4440 mL | 17.2200 mL | 34.4400 mL | |
| 5 mM | 0.6888 mL | 3.4440 mL | 6.8880 mL | |
| 10 mM | 0.3444 mL | 1.7220 mL | 3.4440 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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