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| Targets |
Atrimustine targets estrogen receptor-positive cancer cells. The estradiol benzoate moiety serves as a targeting ligand, allowing the drug to be preferentially taken up by cells that express the estrogen receptor. Once inside the cell, the chlorambucil moiety, which is a DNA alkylating agent, exerts its cytotoxic effect by crosslinking DNA, thereby inhibiting DNA replication and transcription, leading to cell death. This dual mechanism—targeting via the estrogen receptor and cytotoxicity via DNA alkylation—is designed to enhance the antitumor activity of chlorambucil while reducing systemic toxicity.
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| ln Vitro |
Chlorambucil and β-estradiol benzoate combine to form atromustine, often known as bestrabucil. It can strengthen chlorambucil's anti-tumor effect and has a strong affinity for tumor cells [1]. The growth factors generated by the androgen-responsive cultured cancer cell line Shionogi carcinoma 115 (SC-115) were investigated. Using the 3 H-thymidine uptake assay, concentration-dependent suppression of growth factor synthesis by SC-115 cells can be shown at Atrimustine concentrations ranging from 100 nM to 10 μM [2].
In vitro, Atrimustine has been shown to have high affinity for tumor cells and enhances the antitumor activity of chlorambucil. In studies using Shionogi carcinoma 115 (SC-115) cells, an androgen-responsive cultured cancer cell line, Atrimustine at concentrations of 100 nM-10 μM demonstrated concentration-dependent inhibition of growth factor production. At concentrations of 10 μM and 1 μM, it exhibited statistically significant inhibition of SC-115 cell growth. The IC50 for Atrimustine in SC-115 cells was determined to be 10 μM. These findings confirm that Atrimustine is a potent inhibitor of hormone-dependent cancer cell growth in vitro. |
| ln Vivo |
In vivo, Atrimustine has been studied as a treatment for breast cancer and non-Hodgkin's lymphoma. It was designed to treat hormone-dependent cancers by using the estrogen component to enhance uptake into estrogen receptor–positive cells. The compound has been investigated in clinical trials. However, specific in vivo efficacy data, such as tumor regression in animal models or detailed clinical trial results, are not detailed in standard product descriptions. Its use in combination with other agents, such as human lymphoblastoid interferon, has also been explored.
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| Enzyme Assay |
Atrimustine's in vitro activity is typically assessed using cell-based assays. In a typical assay, hormone-dependent cancer cells, such as SC-115 cells, are cultured in the presence of testosterone and treated with varying concentrations of Atrimustine. Cell growth is measured by ³H-thymidine uptake assay, which quantifies DNA synthesis. The IC50 is determined from dose-response curves. The compound's ability to inhibit growth factor production can also be measured. These assays confirm that Atrimustine is a potent inhibitor of hormone-dependent cancer cell growth.
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| Cell Assay |
In vitro cell-based assays for Atrimustine are conducted using hormone-dependent cancer cell lines, such as SC-115 cells. In a typical assay, cells are seeded in multi-well plates and cultured in medium containing 10 nM testosterone. Atrimustine is added at various concentrations, and the cells are incubated for several days. Cell growth is assessed by ³H-thymidine uptake or by using a colorimetric assay such as MTT. The IC50 is determined from dose-response curves. These assays confirm that Atrimustine inhibits the growth of hormone-dependent cancer cells in a concentration-dependent manner.
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| Animal Protocol |
In vivo animal experiments for Atrimustine are not detailed in standard product descriptions. As a compound that was investigated clinically, it would have been evaluated in animal models of cancer. In a typical study, mice bearing xenograft tumors of estrogen receptor-positive breast cancer would be treated with Atrimustine, and tumor growth would be monitored. The compound's ability to inhibit tumor growth and its toxicity profile would be assessed. However, specific protocols are not provided in the available literature. Its use is limited to research applications and historical clinical studies.
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| ADME/Pharmacokinetics |
Atrimustine has a molecular weight of 720.72 g/mol and a molecular formula of C41H47Cl2NO5. It is soluble in DMSO (16.67 mg/mL, 23.13 mM) with ultrasonic warming to 60°C. For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been studied in the context of clinical development.
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| Toxicity/Toxicokinetics |
Atrimustine is an alkylating agent and is expected to have significant toxicity, including myelosuppression, nausea, and vomiting, which are common side effects of DNA-damaging chemotherapeutic agents. Specific toxicity data, such as LD50 or organ toxicity, are not detailed in standard product descriptions. As a DNA alkylating agent, it has the potential for carcinogenicity and teratogenicity. In clinical use, patients would be monitored for hematological toxicity and other adverse effects. As with all research chemicals and pharmaceuticals, it should be handled with caution using appropriate safety measures.
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| References |
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| Additional Infomation |
Atramustine is the benzoate salt of estradiol-chlorinated mustard. (National Cancer Institute)
Atrimustine (Bestrabucil) is a research compound and an antineoplastic drug that has been investigated for the treatment of breast cancer and non-Hodgkin's lymphoma. It is a conjugate of chlorambucil and β-estradiol benzoate designed to target estrogen receptor-positive cancer cells. Its mechanism of action involves the estradiol moiety for targeted uptake and the chlorambucil moiety for DNA alkylation and cytotoxicity. Atrimustine has been studied in clinical trials, including for adult T-cell leukemia-lymphoma. However, it may not be widely used clinically today. It remains a compound of interest for studying targeted chemotherapeutic approaches. |
| Molecular Formula |
C41H47CL2NO6
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|---|---|
| Molecular Weight |
720.7210
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| Exact Mass |
719.278
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| CAS # |
75219-46-4
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| PubChem CID |
6917688
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
804.3±65.0 °C at 760 mmHg
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| Flash Point |
440.2±34.3 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.611
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| LogP |
10.51
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
50
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| Complexity |
1120
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| Defined Atom Stereocenter Count |
5
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| SMILES |
ClC([H])([H])C([H])([H])N(C([H])([H])C([H])([H])Cl)C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])C([H])([H])C(=O)OC([H])([H])C(=O)O[C@@]1([H])C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4C([H])=C(C([H])=C([H])C=4[C@@]3([H])C([H])([H])C([H])([H])[C@@]21C([H])([H])[H])OC(C1C([H])=C([H])C([H])=C([H])C=1[H])=O
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| InChi Key |
IFJUINDAXYAPTO-UUBSBJJBSA-N
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| InChi Code |
InChI=1S/C41H47Cl2NO6/c1-41-21-20-34-33-17-15-32(49-40(47)29-7-3-2-4-8-29)26-30(33)12-16-35(34)36(41)18-19-37(41)50-39(46)27-48-38(45)9-5-6-28-10-13-31(14-11-28)44(24-22-42)25-23-43/h2-4,7-8,10-11,13-15,17,26,34-37H,5-6,9,12,16,18-25,27H2,1H3/t34-,35-,36+,37+,41+/m1/s1
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| Chemical Name |
[(8R,9S,13S,14S,17S)-17-[2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butanoyloxy]acetyl]oxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] benzoate
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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 : ~16.67 mg/mL (~23.13 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 | 1.3875 mL | 6.9375 mL | 13.8750 mL | |
| 5 mM | 0.2775 mL | 1.3875 mL | 2.7750 mL | |
| 10 mM | 0.1388 mL | 0.6938 mL | 1.3875 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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