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| 2mg |
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| 5mg |
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| 10mg |
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| Targets |
Anti-tumor antibiotic; ADC cytotoxin
N-Acetyl-Calicheamicin targets DNA, specifically binding to the minor groove of DNA and causing double-strand breaks. The compound's enediyne core undergoes a Bergman cyclization to form a diradical species that abstracts hydrogen atoms from the deoxyribose sugar backbone of DNA, leading to strand scission. The compound's DNA-binding domain targets specific DNA sequences, and the cleavage of DNA results in the activation of the DNA damage response, leading to cell cycle arrest and apoptosis. N-Acetyl-Calicheamicin is highly cytotoxic and is used as a payload in ADCs for the targeted delivery of the drug to cancer cells. In ADCs, the compound is conjugated to a monoclonal antibody that targets a tumor-specific antigen, allowing for the selective delivery of the cytotoxic payload to cancer cells while minimizing systemic toxicity. The compound's mechanism of action is similar to other enediyne antibiotics, such as neocarzinostatin and esperamicin, which also cause DNA strand scission. |
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| ln Vitro |
In vitro studies have demonstrated that N-Acetyl-Calicheamicin is a potent cytotoxic agent that induces apoptosis in a variety of cancer cell lines. The compound causes DNA double-strand breaks, leading to the activation of ATM/ATR, the phosphorylation of H2AX, and the activation of the p53 pathway. The IC₅₀ values for N-Acetyl-Calicheamicin in cancer cell lines are typically in the picomolar to low nanomolar range, reflecting its extreme potency. In cell viability assays, the compound induces cell death in a concentration- and time-dependent manner, with apoptosis being the primary mode of cell death. The compound's cytotoxicity is dependent on its ability to bind to DNA and cause strand scission, and cells that are deficient in DNA repair pathways are more sensitive to the compound's effects. In combination with other anticancer agents, N-Acetyl-Calicheamicin has been shown to have synergistic effects, enhancing the efficacy of chemotherapy and radiation therapy. The compound's selectivity for cancer cells is enhanced by its conjugation to tumor-targeting antibodies in ADCs.
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| ln Vivo |
In vivo studies have demonstrated the efficacy of N-Acetyl-Calicheamicin-containing ADCs in animal models of cancer. In mouse xenograft models of AML, non-Hodgkin lymphoma, and other cancers, ADCs containing N-Acetyl-Calicheamicin have been shown to induce complete tumor regression and prolong survival. The targeted delivery of the compound via ADCs reduces systemic toxicity and enhances the therapeutic index of the drug. The compound's efficacy in vivo is dose-dependent, and the maximum tolerated dose is determined by the toxicity of the payload and the targeting properties of the antibody. In clinical studies, N-Acetyl-Calicheamicin-containing ADCs, such as gemtuzumab ozogamicin (Mylotarg), have been approved for the treatment of AML, demonstrating the clinical utility of the compound. However, the compound's use is associated with significant toxicity, including hepatotoxicity and myelosuppression, which limit its clinical application.
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| Enzyme Assay |
For in vitro cytotoxicity assays, N-Acetyl-Calicheamicin is tested against a panel of cancer cell lines, including AML (e.g., HL-60, THP-1), lymphoma (e.g., Ramos, Daudi), and solid tumor cell lines (e.g., breast, ovarian, lung). Cells are seeded in 96-well plates at 5 × 10³ cells per well and treated with the compound at concentrations of 0.001-100 nM for 48-72 hours. Cell viability is determined using MTT, CellTiter-Glo, or other cell viability assays. The IC₅₀ is determined from dose-response curves. For apoptosis assays, cells are treated with the compound for 24-48 hours, and apoptosis is assessed by flow cytometry using Annexin V-FITC/PI staining, caspase-3/7 activity assays, and Western blot analysis of apoptosis-related proteins. For DNA damage assays, cells are treated with the compound, and the phosphorylation of H2AX (γH2AX) is measured by Western blotting or by immunofluorescence. All experiments include appropriate positive and negative controls, and results are expressed as mean ± standard deviation from at least three independent experiments.
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| Animal Protocol |
For in vivo animal experiments, N-Acetyl-Calicheamicin is typically administered as an ADC to mice in tumor xenograft models. Immunocompromised mice (e.g., BALB/c nude, SCID, NSG) are subcutaneously or intravenously inoculated with 1 × 10⁶ to 5 × 10⁶ tumor cells (e.g., HL-60, Ramos). When tumors reach a volume of 50-100 mm³, mice are randomized into treatment groups (n=6-8 per group) and administered the ADC intravenously at doses of 0.1-5 mg/kg (based on payload content) on a once-weekly or biweekly schedule for 2-4 weeks. Tumor volume is measured every 2-3 days, and body weights are recorded daily. At the end of the study, tumors are excised, weighed, and processed for histopathological analysis. Blood samples are collected for pharmacokinetic analysis and for the measurement of hematological parameters. For toxicology studies, the compound is administered to mice or rats, and parameters such as body weight, organ weights, hematology, serum biochemistry, and histopathology are assessed. All animal procedures are conducted in accordance with institutional guidelines for the care and use of laboratory animals.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for N-Acetyl-Calicheamicin are primarily derived from studies of ADCs containing the compound. The compound has a molecular weight of approximately 1410.39-1410.41 g/mol and a molecular formula of C₅₇H₇₆IN₃O₂₂S₄. When administered as an ADC, the pharmacokinetics of the compound are determined by the antibody, with a long half-life (days) and low clearance. The compound is released from the ADC in the tumor microenvironment or upon internalization into cancer cells, and it is rapidly metabolized and cleared. The compound's toxicity is primarily due to its effects on DNA in rapidly dividing cells, including bone marrow cells and gastrointestinal epithelial cells.
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| Toxicity/Toxicokinetics |
The toxicity of N-Acetyl-Calicheamicin is significant, and its use is associated with myelosuppression, hepatotoxicity, and other adverse effects. In preclinical toxicology studies, the compound causes dose-dependent bone marrow suppression, liver enzyme elevations, and gastrointestinal toxicity. The compound is a potent cytotoxin, and its use is limited by its narrow therapeutic index. In clinical studies, the compound's toxicity has been managed by dose reduction, supportive care, and the use of targeted delivery via ADCs. As with all research chemicals, appropriate safety precautions should be taken when handling N-Acetyl-Calicheamicin, including the use of personal protective equipment and working in a well-ventilated fume hood. The compound is for research use only and is not intended for human therapeutic use outside of approved ADC formulations.
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| References | |
| Additional Infomation |
Getruzumab ozomicin (GO) is a chemotherapy drug composed of a humanized anti-CD33 antibody (hP67.6) linked to the potent enediyne antibiotic N-acetylcalic acid 1,2-dimethylhydrazine dichloride. In May 2000, the U.S. Food and Drug Administration (FDA) conditionally approved GO as monotherapy for the treatment of first-relapsed acute myeloid leukemia (AML) patients aged 60 years and older who were ineligible for conventional cytotoxic therapy. Under this indication, the complete remission (CR) rate with GO was 13%, with an additional 13% of patients achieving complete remission but with insufficient platelet recovery (CRp). The most common adverse reactions to GO are infusion-related reactions and myelosuppression. Approximately 5% of patients treated with Golov monotherapy (at a dose of 9 mg/m²) experience hepatic vein occlusion, especially before and after stem cell transplantation. Reducing the dose of Golov monotherapy or administering it in divided doses appears to be equally effective and better tolerated. Golov monotherapy has shown significant efficacy in acute promyelocytic leukemia, particularly in clearing minimal residual disease. Golov monotherapy in combination with chemotherapy shows promise as an induction therapy or post-remission treatment regimen and is currently undergoing phase III clinical trials. [1]
N-Acetyl-Calicheamicin is a research-use only compound and is a component of FDA-approved ADCs for the treatment of cancer. It is also known as N-Acetyl-Calicheamicin γ and is a potent enediyne antitumor antibiotic. The compound has a molecular formula of C₅₇H₇₆IN₃O₂₂S₄ and a molecular weight of approximately 1410.39-1410.41 g/mol. N-Acetyl-Calicheamicin is a derivative of calicheamicin and is used as a cytotoxic payload in ADCs for the targeted treatment of hematologic malignancies and solid tumors. The compound is available from various research chemical suppliers for non-clinical studies. Storage recommendations include keeping the compound in a tightly sealed container, protected from light and moisture, at 2-8°C. |
| Molecular Formula |
C57H76IN3O22S4
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|---|---|
| Molecular Weight |
1410.38472557068
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| Exact Mass |
1409.28
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| Elemental Analysis |
C, 48.54; H, 5.43; I, 9.00; N, 2.98; O, 24.96; S, 9.09
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| CAS # |
108212-76-6
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| Related CAS # |
Calicheamicin;108212-75-5
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| PubChem CID |
134819845
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| Appearance |
White to off-white solid powder
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| LogP |
2
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
27
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
87
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| Complexity |
2640
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| Defined Atom Stereocenter Count |
19
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| SMILES |
CCN([C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\C#C[C@@]4(CC(=O)C(=C3C4=CCSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O)C(=O)C
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| InChi Key |
WPDOZYZAJKUVRZ-DPACUSKXSA-N
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| InChi Code |
InChI=1S/C57H76IN3O22S4/c1-13-61(30(6)62)32-25-76-37(23-36(32)71-7)81-50-45(66)42(27(3)78-55(50)80-35-18-16-14-15-17-20-57(70)24-34(64)43(59-56(69)75-11)40(35)31(57)19-21-85-87-84-12)60-83-38-22-33(63)52(29(5)77-38)86-53(68)39-26(2)41(58)48(51(74-10)47(39)72-8)82-54-46(67)49(73-9)44(65)28(4)79-54/h14-15,19,27-29,32-33,35-38,42,44-46,49-50,52,54-55,60,63,65-67,70H,13,21-25H2,1-12H3,(H,59,69)/b15-14-,31-19-/t27-,28+,29-,32+,33+,35+,36+,37+,38+,42-,44+,45+,46-,49-,50-,52-,54+,55+,57+/m1/s1
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| Chemical Name |
S-((2R,3S,4S,6S)-6-((((2R,3S,4S,5R,6R)-5-(((2S,4S,5S)-5-(N-ethylacetamido)-4-methoxytetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(((2S,5Z,9R,13Z)-9-hydroxy-12-((methoxycarbonyl)amino)-13-(2-(methyltrisulfanyl)ethylidene)-11-oxobicyclo[7.3.1]trideca-1(12),5-dien-3,7-diyn-2-yl)oxy)-2-methyltetrahydro-2H-pyran-3-yl)amino)oxy)-4-hydroxy-2-methyltetrahydro-2H-pyran-3-yl)
4-(((2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzothioate
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| Synonyms |
N-Acetyl calicheamicin; N-Acetyl-Calicheamicin; 108212-76-6; N-Acetyl-γ-calicheamicin; N-Acetylcalicheamicin γ;
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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, 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) |
DMSO : ~100 mg/mL (~70.90 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 | 0.7090 mL | 3.5451 mL | 7.0902 mL | |
| 5 mM | 0.1418 mL | 0.7090 mL | 1.4180 mL | |
| 10 mM | 0.0709 mL | 0.3545 mL | 0.7090 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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