| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
DNA (minor groove). Duocarmycins are potent DNA alkylating agents that bind to the minor groove of DNA with high sequence selectivity (preferring AT-rich sequences) and alkylate adenine residues at the N3 position, leading to irreversible DNA damage, cell cycle arrest, and cell death. Seco-DUBA itself is a prodrug and requires activation to the active DUBA form.
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| ln Vitro |
Seco-DUBA (SK-BR-3 cells; 0.0001 pM~0.01 nM; 144 hours) exhibits potency and efficacy comparable to DUBA, albeit at a dose-dependent reduction in cell viability[1]. SK-BR-3 (IC50=0.09), SK-OV-3 (IC50=0.43), and SW620 (IC50=0.09) cells exhibit great sensitivity when exposed to seco-DUBA[1].
Seco-DUBA is a prodrug and lacks direct cytotoxic activity until converted to DUBA. The active DUBA toxin is a highly potent cytotoxic agent, with IC50 values in the picomolar to low nanomolar range against cancer cell lines (typically 10-100 pM). As a prodrug, its activity is dependent on intracellular activation and release from the ADC. When conjugated to a targeting antibody, the ADC delivers the prodrug specifically to tumor cells, where it is activated intracellularly, releasing the potent DUBA toxin and causing targeted tumor cell death. |
| ln Vivo |
Seco-DUBA (89 μg/kg; iv) is likely transformed to DUBA virtually instantaneously[1].
In vivo, seco-DUBA is used as a payload in ADCs. When conjugated to a targeting antibody, the ADC accumulates in tumors via antigen-mediated binding and is internalized. The prodrug is cleaved and activated intracellularly, releasing the potent DUBA toxin and causing tumor cell death. This approach significantly improves the therapeutic index by reducing systemic toxicity compared to administration of the free toxin. ADCs containing duocarmycin payloads have shown potent antitumor activity in mouse xenograft models. |
| Enzyme Assay |
Not applicable for the prodrug itself. The activity of the released DUBA toxin can be assessed in cell-free DNA alkylation assays: isolated plasmid DNA or calf thymus DNA is incubated with DUBA (0.1-100 nM) in TE buffer for 1-24 hours at 37degC. DNA alkylation is detected by changes in DNA mobility on agarose gels, by ethidium bromide displacement, or by HPLC-MS analysis of alkylated nucleosides.
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| Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: SK-BR-3 cells Tested Concentrations: 0.0001 pM~0.01 nM Incubation Duration: 144 hrs (hours) Experimental Results: Dose-dependent decreased cell viability. Cell viability assay: Cancer cells expressing the target antigen are seeded in 96-well plates and treated with the ADC containing seco-DUBA (0.001-1000 nM) or the free DUBA toxin for 72-96 hours. Cell viability is measured using MTT, CellTiter-Glo, or colony formation assays. IC50 values are determined from dose-response curves. Target-dependent killing (comparison with antigen-negative cells) confirms ADC specificity. |
| Animal Protocol |
Animal/Disease Models: Wistar rats[1]
Doses: 89 μg/kg (pharmacokinetic/PK Analysis) Route of Administration: Iv Experimental Results: Likely converted to DUBA almost instantaneously. Mouse xenograft models: Immunodeficient mice bearing human tumor xenografts expressing the target antigen are treated with the ADC containing seco-DUBA (1-10 mg/kg, intravenous, single or multiple doses). Tumor volumes are measured twice weekly, and tumor growth inhibition (TGI) is calculated. Pharmacodynamic analysis includes assessment of DNA damage markers (gamma-H2AX) in tumor tissues. |
| ADME/Pharmacokinetics |
Not applicable for seco-DUBA itself. The pharmacokinetics of ADCs containing seco-DUBA are determined by the antibody component, with a long half-life (typically several days in rodents, 1-3 weeks in humans), low clearance, and limited tissue distribution characteristic of monoclonal antibodies. The drug-to-antibody ratio (DAR) and linker stability influence the release kinetics of the payload.
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| Toxicity/Toxicokinetics |
As a prodrug, seco-DUBA is designed to be less toxic than the active DUBA toxin, reducing off-target effects. Toxicity is primarily associated with the released DUBA toxin, which can cause myelosuppression (neutropenia, thrombocytopenia), gastrointestinal effects, and potential liver toxicity at high doses. The ADC approach aims to minimize systemic toxicity by delivering the payload specifically to tumor cells.
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| References | |
| Additional Infomation |
This is a research compound used in ADC development. It is a duocarmycin-based payload that allows for the creation of stable and potent ADCs. The presence of two hydroxyl groups enables site-specific conjugation to antibodies via various linker chemistries, including maleimide-thiol chemistry and click chemistry. Also known as a DUBA (Duocarmycin DUBA) prodrug.
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| Molecular Formula |
C29H23CLN4O4
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|---|---|
| Molecular Weight |
526.97
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| Exact Mass |
526.14
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| CAS # |
1227961-59-2
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| Related CAS # |
Seco-DUBA hydrochloride;1795733-93-5
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| PubChem CID |
46240929
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| Appearance |
Light yellow to brown solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
38
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| Complexity |
885
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(NC1=CN2C=C(C(N3C4=C(C5=C(C)C=CC=C5C(O)=C4)[C@H](CCl)C3)=O)N=C2C=C1)(=O)C1=CC=C(O)C=C1
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| InChi Key |
VQAFBYLFRCCWNB-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C29H23ClN4O4/c1-16-3-2-4-21-24(36)11-23-27(26(16)21)18(12-30)13-34(23)29(38)22-15-33-14-19(7-10-25(33)32-22)31-28(37)17-5-8-20(35)9-6-17/h2-11,14-15,18,35-36H,12-13H2,1H3,(H,31,37)/t18-/m1/s1
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| Chemical Name |
N-[2-[(1S)-1-(chloromethyl)-5-hydroxy-9-methyl-1,2-dihydrobenzo[e]indole-3-carbonyl]imidazo[1,2-a]pyridin-6-yl]-4-hydroxybenzamide
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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 : 100 mg/mL (189.76 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (1.90 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: 1 mg/mL (1.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8976 mL | 9.4882 mL | 18.9764 mL | |
| 5 mM | 0.3795 mL | 1.8976 mL | 3.7953 mL | |
| 10 mM | 0.1898 mL | 0.9488 mL | 1.8976 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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