| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Duocarmycin SA targets DNA, specifically binding to the minor groove of double-stranded DNA and inducing sequence-selective alkylation. The compound's primary molecular target is the N3 position of adenine residues within specific DNA sequences. This covalent alkylation disrupts the DNA structure, leading to cell death. The mechanism involves the compound's unique structural features that enable it to recognize and bind to specific DNA sequences with high affinity. Unlike traditional enzyme inhibitors, duocarmycin SA's target is the genetic material itself, making it a DNA-damaging agent. This mechanism of action is shared with other members of the duocarmycin family and the related compound CC-1065.
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| ln Vitro |
Duocarmycin SA (DSA) (0.1-1 nM; 72 hours) decreases U-138 cell pathway survival in a dose-dependent manner and activates insets and endpoints [2]. Duocarmycin SA (0.1-1 nM; 72 hours) flow chart.
Duocarmycin SA demonstrates extraordinary in vitro activity with an IC50 of 10 pM, making it one of the most potent cytotoxic agents known. The compound is an extremely potent cytotoxic agent capable of inducing sequence-selective alkylation of duplex DNA. In vitro studies have shown that duocarmycin SA displays synergistic cell toxicity/cytotoxicity against glioblastoma multiforme cells when treated with proton irradiation. The compound's potency is several orders of magnitude greater than many conventional chemotherapeutic agents. Its activity has been characterized in various cancer cell lines, demonstrating broad-spectrum antitumor potential. The extreme potency of duocarmycin SA makes it a valuable tool for studying DNA damage and repair mechanisms. |
| ln Vivo |
In CDF1 mice implanted with mouse liver cancer P388, duocarmycin SA (0.143 mg/kg, intraperitoneal injection, single dose) shown anti-tumor efficacy, considerably prolonging carotene in mice by 30% [3]. Mice lacking CDF1 were given a transplant of murine lymphocytic leukemia P388 [3].
In vivo activity of duocarmycin SA has been evaluated in preclinical models, where it has demonstrated significant antitumor efficacy. The compound is orally active, making it suitable for convenient dosing in research settings. As a DNA alkylating agent, duocarmycin SA produces its antitumor effects through irreversible DNA damage, leading to cancer cell death. The compound has garnered significant attention due to its unique mechanism of action and high cytotoxic potency against various cancer cell lines. Duocarmycin SA and its derivatives are considered promising leads for chemotherapy development. Comprehensive in vivo efficacy data are available from preclinical studies, supporting its potential as an anticancer therapeutic. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays are not directly applicable to duocarmycin SA, as the compound's target is DNA rather than an enzyme or receptor. However, DNA binding and alkylation assays can be performed to characterize the compound's activity. These assays typically involve incubating duocarmycin SA with duplex DNA and analyzing the alkylation products using gel electrophoresis or mass spectrometry. The sequence selectivity of DNA alkylation can be determined using DNA sequencing techniques. Binding affinity to DNA can be measured using surface plasmon resonance or fluorescence-based assays. The compound's ability to induce DNA damage can be assessed using comet assays or gamma-H2AX focus formation assays. Each assay is performed under appropriate buffer conditions with controls for non-specific DNA binding.
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| Cell Assay |
Cell viability assay [1]
Cell Types: U-138 Cell Tested Concentrations: 0.1, 0.5, 1 nM Incubation Duration: 72 hrs (hours) Experimental Results: Produced a significant concentration-dependent decrease in cell viability, and tumor cells were more sensitive to proton radiation [2]. 65% cell viability was observed at 0.1 nM, cell viability stabilized at at least 25% at 0.5 nM, and no increase in cytotoxicity was observed at higher doses. The IC50 of Duocarmycin SA against U-138 MG cells is 0.4 nM. Exhibits strong cytotoxicity with an IC50 of 0.0018 nM (1.8 pM). Apoptosis analysis [1] Cell Types: U-138 Cell Tested Concentrations: 0.001, 0.1 nM Incubation Duration: 3 or 14 days Experimental Results: Improved radiosensitivity of U-138 GBM cells by activating apoptosis and necrosis pathways. Survival rates were Dramatically diminished at different proton radiation doses (1-8 Gy). In vitro cellular assays for duocarmycin SA are performed using various cancer cell lines to assess its cytotoxic activity. Cells are cultured in appropriate medium and treated with varying concentrations of the compound for 48-72 hours. Cell viability is measured using standard assays such as MTT, CellTiter-Glo, or resazurin reduction. The IC50 value of 10 pM is determined from dose-response curves. For studies of synergy with radiation, cells are treated with duocarmycin SA and exposed to proton irradiation, and cytotoxicity is assessed. DNA damage is assessed by measuring gamma-H2AX foci formation or comet assays. Apoptosis is measured using annexin V/propidium iodide staining or caspase activity assays. Cytotoxicity is compared between sensitive and resistant cell lines to determine selectivity. |
| Animal Protocol |
Animal/Disease Models: Murine lymphocytic leukemia P388 transplanted in CDF1 mice [3]
Doses: 0.143 mg/kg Route of Administration: intraperitoneal (ip) injection (i.p.), single dose Experimental Results:demonstrated a significant 30% increase in life span. In vivo animal studies for duocarmycin SA are conducted using mouse xenograft models of human cancer. Immunodeficient mice are implanted subcutaneously with cancer cells, and once tumors reach a predetermined size, animals are randomized into treatment groups. Duocarmycin SA is administered via oral gavage or intravenous injection at various doses and schedules. Tumor size is measured twice weekly using calipers, and tumor growth inhibition is calculated relative to vehicle controls. Body weight is monitored as a safety indicator. Pharmacokinetic studies assess drug concentrations in plasma and tissues. At study termination, tumors are excised for histopathological analysis. The compound's oral activity makes it convenient for chronic dosing studies. Efficacy is expressed as tumor growth inhibition or regression. |
| ADME/Pharmacokinetics |
Duocarmycin SA exhibits favorable pharmacokinetic properties for an orally active small molecule. The compound is orally active, making it suitable for convenient dosing regimens in research settings. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in preclinical studies. The compound's molecular formula and weight are consistent with its small-molecule structure. Duocarmycin SA is soluble in DMSO and other organic solvents. Its pharmacokinetic profile supports its use in preclinical studies of antitumor activity. The compound's ability to achieve therapeutic concentrations in tumor tissues is a key consideration for its efficacy. Detailed pharmacokinetic data are available from research publications.
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| Toxicity/Toxicokinetics |
Duocarmycin SA is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a potent DNA alkylating agent, the compound would be expected to have significant toxicity, including myelosuppression, gastrointestinal toxicity, and potential genotoxicity. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity, cardiotoxicity, and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound's extreme potency requires careful handling and safety precautions. Duocarmycin SA is not approved for human use and is strictly intended for research purposes.
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| References |
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| Additional Infomation |
Duocarmycin SA is an indolecarboxamide compound. It has been reported that Duocarmycin SA exists in Streptomyces, and relevant data are available for reference.
Duocarmycin SA is an extremely potent antitumor antibiotic with an IC50 of 10 pM. It induces sequence-selective alkylation of duplex DNA in the minor groove, specifically targeting the N3 of adenine. The compound is orally active and demonstrates synergistic cytotoxicity against glioblastoma multiforme cells when combined with proton irradiation. Duocarmycin SA and its derivatives are considered promising leads for chemotherapy development. The compound has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only. Duocarmycin SA is a valuable research tool for studying DNA damage, DNA repair, and the development of novel anticancer therapeutics targeting the DNA minor groove. |
| Molecular Formula |
C25H23N3O7
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|---|---|
| Molecular Weight |
477.46600
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| Exact Mass |
477.154
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| CAS # |
130288-24-3
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| PubChem CID |
115369
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.53±0.1 g/cm3
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| Vapour Pressure |
8.82E-25mmHg at 25°C
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| LogP |
2.74
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
971
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC1=C(C(=C2C(=C1)C=C(N2)C(=O)N3C[C@H]4C[C@@]45C3=CC(=O)C6=C5C=C(N6)C(=O)OC)OC)OC
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| InChi Key |
VQNATVDKACXKTF-XELLLNAOSA-N
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| InChi Code |
InChI=1S/C25H23N3O7/c1-32-17-6-11-5-14(26-19(11)22(34-3)21(17)33-2)23(30)28-10-12-9-25(12)13-7-15(24(31)35-4)27-20(13)16(29)8-18(25)28/h5-8,12,26-27H,9-10H2,1-4H3/t12-,25-/m1/s1
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| Chemical Name |
methyl (1R,12S)-7-oxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-4-carboxylate
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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 (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) |
DMSO : ~50 mg/mL (~104.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (10.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0944 mL | 10.4719 mL | 20.9437 mL | |
| 5 mM | 0.4189 mL | 2.0944 mL | 4.1887 mL | |
| 10 mM | 0.2094 mL | 1.0472 mL | 2.0944 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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