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| Targets |
Duocarmycin targets DNA by binding to the minor groove and alkylating adenine residues at N3 position in a sequence-specific manner. This DNA alkylation causes irreversible DNA damage, leading to cell cycle arrest and apoptosis. The unique mechanism of action is responsible for its potent anticancer activity.
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| ln Vitro |
Members of the class of DNA minor groove, AT sequence-selective, and adenine-N3 alkylating compounds that were identified from the genus Streptomyces include duocarmycins and CC-1065. It shows incredibly potent cytotoxicity against the proliferation of cancer cells cultured in vitro [2]. With IC50s of 22, 13.8, 3.87, 15.4, and 7.31 pM for HT-29, CL1-5, Caski, EJ, and LS174T, respectively, duocarmycin is cytotoxic to a range of human cancer cells [3].
In vitro, Duocarmycin exhibits potent cytotoxic activity against various cancer cell lines by inducing DNA damage via sequence-specific alkylation in the minor groove. It is highly potent, with IC50 values in the picomolar to nanomolar range against many tumor cell types. Its unique structure enables potent anticancer activity. |
| ln Vivo |
In vivo, Duocarmycin demonstrates antitumor efficacy in preclinical models when delivered as an ADC payload. The antibody component targets tumor-specific antigens, delivering the cytotoxic Duocarmycin directly to cancer cells. This targeted approach enhances efficacy and reduces systemic toxicity.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays are not applicable for Duocarmycin, as its mechanism involves direct DNA alkylation rather than enzyme or receptor binding. DNA binding assays are performed using purified DNA or oligonucleotides, and alkylation is detected by gel electrophoresis, mass spectrometry, or fluorescence-based methods.
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| Cell Assay |
Cellular assays for Duocarmycin are conducted using cancer cell lines from various tumor types. Cells are treated with serial dilutions of the compound (0.01 pM to 100 nM) for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. DNA damage is evaluated by comet assay or gamma-H2AX foci formation. Apoptosis is measured by Annexin V/PI staining.
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| Animal Protocol |
In vivo efficacy studies for Duocarmycin ADCs are conducted in xenograft mouse models bearing human tumor xenografts expressing the target antigen. The ADC is administered via intravenous injection at doses typically ranging from 0.1-10 mg/kg on a weekly or bi-weekly schedule. Tumor volume is measured, and TGI is calculated. Pharmacodynamic markers including DNA damage are assessed in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Duocarmycin as an ADC payload are characterized by the ADC's overall PK profile. The compound has a molecular weight of 463.96 and formula C26H26ClN3O3. It is soluble in DMSO and stored at -20degC. As a free base, it is not administered systemically without conjugation.
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| Toxicity/Toxicokinetics |
Toxicological data for Duocarmycin indicate that as a potent DNA alkylator, it has significant cytotoxic potential. When delivered as an ADC, the toxicity profile is largely determined by the targeting antibody and linker stability. Off-target toxicity may include myelosuppression and gastrointestinal effects. Standard toxicology assessments are conducted for each ADC candidate.
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| References |
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| Additional Infomation |
Duocarmycin is a research-use compound not approved as a standalone therapeutic. It is widely used as a potent ADC payload in cancer research. The compound's unique DNA alkylation mechanism makes it a valuable tool for studying DNA damage responses and developing targeted cancer therapies. It is for research use only and not for human therapeutic application.
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| Molecular Formula |
C26H26CLN3O3
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|---|---|
| Molecular Weight |
463.9559
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| Exact Mass |
463.166
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| CAS # |
1116745-06-2
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| Related CAS # |
Duocarmycin DM
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| PubChem CID |
56675231
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
694
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC([H])([H])[C@]1([H])C([H])([H])N(C(C2=C([H])C3C([H])=C(C([H])=C([H])C=3N2[H])OC([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O)C2C([H])=C(C3=C([H])C([H])=C([H])C([H])=C3C1=2)O[H]
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| InChi Key |
JRGWJJXUVWWGDA-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C26H26ClN3O3/c1-29(2)9-10-33-18-7-8-21-16(11-18)12-22(28-21)26(32)30-15-17(14-27)25-20-6-4-3-5-19(20)24(31)13-23(25)30/h3-8,11-13,17,28,31H,9-10,14-15H2,1-2H3/t17-/m1/s1
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| Chemical Name |
[(1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1H-indol-2-yl]methanone
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 (~107.77 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 | 2.1554 mL | 10.7768 mL | 21.5536 mL | |
| 5 mM | 0.4311 mL | 2.1554 mL | 4.3107 mL | |
| 10 mM | 0.2155 mL | 1.0777 mL | 2.1554 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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