| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of MC-Val-Cit-PAB-duocarmycin, as an ADC drug-linker conjugate, is the specific antigen expressed on the surface of target cancer cells, to which the antibody component of the ADC binds. The cytotoxic payload, duocarmycin, is a DNA minor groove-binding alkylating agent that alkylates adenine residues in the minor groove of DNA. Upon binding of the ADC to the target antigen, the conjugate is internalized, and the linker is cleaved to release duocarmycin, which then alkylates DNA and induces cell death. The MC-Val-Cit-PAB linker is designed to be cleaved by cathepsins in the lysosome, ensuring selective release of the payload inside target cells.
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| ln Vitro |
In vitro studies of MC-Val-Cit-PAB-duocarmycin are focused on evaluating its cytotoxicity against target cells and its stability in biological fluids. As an ADC drug-linker conjugate, the compound's activity is typically assessed in cell-based cytotoxicity assays using target antigen-positive and antigen-negative cell lines. The conjugate is expected to show potent antitumor activity against target-positive cells while sparing antigen-negative cells. Duocarmycin is an extremely potent cytotoxic agent, and its targeted delivery via the ADC linker is designed to minimize systemic toxicity. The compound's stability in plasma and its ability to release duocarmycin upon internalization are also evaluated.
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| ln Vivo |
In vivo studies of MC-Val-Cit-PAB-duocarmycin are focused on evaluating the antitumor efficacy and pharmacokinetics of ADCs constructed with this drug-linker conjugate. The compound is used in the development of ADCs for targeted cancer therapy. In xenograft models, ADCs containing MC-Val-Cit-PAB-duocarmycin are expected to show potent antitumor activity with improved pharmacokinetics and a better therapeutic index compared to unconjugated duocarmycin. The conjugate is designed to achieve selective delivery of the potent duocarmycin payload to tumor cells, thereby enhancing efficacy and reducing off-target toxicity. Further studies are needed to fully characterize the in vivo efficacy and safety of ADCs containing this drug-linker conjugate.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, MC-Val-Cit-PAB-duocarmycin is not typically used in direct binding assays, as it is a drug-linker conjugate rather than a small molecule drug. However, the stability of the linker and the release of duocarmycin can be assessed in vitro using enzymatic or chemical cleavage assays. The compound is incubated with cathepsins or other lysosomal enzymes, and the release of duocarmycin is quantified by HPLC or LC-MS. The binding of the ADC to its target antigen is typically assessed using the full ADC construct, not the drug-linker conjugate alone. Standard assay conditions include physiological buffer systems with appropriate pH to mimic the lysosomal environment.
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| Cell Assay |
For in vitro cellular experiments, MC-Val-Cit-PAB-duocarmycin is typically evaluated as part of a complete ADC. The ADC is tested in target antigen-positive and antigen-negative cell lines to assess target-specific cytotoxicity. Cells are cultured in appropriate media and treated with various concentrations of the ADC. Cell viability is assessed using MTT, CellTiter-Glo, or other cytotoxicity assays. The selectivity of the ADC for target-positive cells is a key measure of its therapeutic potential. Duocarmycin is a highly potent DNA alkylating agent, and its effects on cell cycle and DNA damage can be assessed using gamma-H2AX staining or comet assays. Internalization and release of duocarmycin can be assessed using fluorescently labeled antibodies or by measuring free duocarmycin in cell lysates.
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| Animal Protocol |
For in vivo animal experiments, MC-Val-Cit-PAB-duocarmycin is used to construct ADCs that are administered to tumor-bearing mice. Xenograft models using human cancer cell lines that express the target antigen are commonly used. The ADC is typically administered via intravenous injection at various doses and schedules. Tumor volume is measured regularly, and tumor growth inhibition is calculated. Pharmacokinetic studies are performed to measure the levels of ADC, total antibody, and released duocarmycin in plasma. Tissue distribution studies may also be conducted. Body weight and overall health are monitored as indicators of tolerability. The potent antitumor activity of duocarmycin and the targeted delivery provided by the ADC are key outcomes of these studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MC-Val-Cit-PAB-duocarmycin as a drug-linker conjugate are designed to improve the pharmacokinetics of the potent duocarmycin payload. When administered as part of an ADC, the conjugate is expected to have a longer half-life in circulation and improved tumor accumulation compared to the free drug. The release of duocarmycin from the linker is designed to occur preferentially inside target cells, reducing systemic exposure and toxicity. Detailed pharmacokinetic parameters would depend on the specific ADC construct and the target antigen. The linker's stability in circulation is critical for achieving selective delivery.
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| Toxicity/Toxicokinetics |
Toxicological data for MC-Val-Cit-PAB-duocarmycin are limited, as it is a research tool for ADC development. The toxicity of ADCs containing this drug-linker conjugate would depend on the target antigen expression profile, the extreme potency of duocarmycin, and the stability of the linker. Duocarmycin is a highly potent DNA alkylating agent, and off-target release could cause significant toxicity, including myelosuppression and other severe adverse effects. The selectivity of the ADC for target-positive cells is critical for minimizing toxicity. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines for handling potent cytotoxic agents.
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| References | |
| Additional Infomation |
MC-Val-Cit-PAB-duocarmycin is a research compound used for ADC development. No clinical trials or regulatory approvals have been reported for this specific drug-linker conjugate as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound combines the potent DNA minor groove-binding alkylating agent duocarmycin with the MC-Val-Cit-PAB ADC linker. It is used in the development of ADCs for targeted cancer therapy. The conjugate exhibits significant antitumor activity and is an antibody-conjugated active molecule.
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| Molecular Formula |
C54H65CLN9O9
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|---|---|
| Molecular Weight |
1019.60181212425
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| Exact Mass |
1053.428
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| CAS # |
2055896-98-3
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| PubChem CID |
162640779
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
74
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| Complexity |
1950
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C([C@@H]1CN(C(C2NC3=CC=C(OCC[N+](C)(C)CC4C=CC(NC(=O)[C@H](CCCNC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN5C(C=CC5=O)=O)=CC=4)C=C3C=2)=O)C2C=C(O)C3=CC=CC=C3C1=2)Cl
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| InChi Key |
UNCKJRMATSMWHA-QMUBXYOZSA-N
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| InChi Code |
InChI=1S/C54H64ClN9O9.ClH/c1-33(2)50(61-46(66)14-6-5-9-24-62-47(67)21-22-48(62)68)52(70)60-42(13-10-23-57-54(56)72)51(69)58-37-17-15-34(16-18-37)32-64(3,4)25-26-73-38-19-20-41-35(27-38)28-43(59-41)53(71)63-31-36(30-55)49-40-12-8-7-11-39(40)45(65)29-44(49)63;/h7-8,11-12,15-22,27-29,33,36,42,50H,5-6,9-10,13-14,23-26,30-32H2,1-4H3,(H7-,56,57,58,59,60,61,65,66,69,70,71,72);1H/t36-,42+,50+;/m1./s1
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| Chemical Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl-[2-[[2-[(1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carbonyl]-1H-indol-5-yl]oxy]ethyl]-dimethylazanium;chloride
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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. (3). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 : ~130 mg/mL (~123.22 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 | 0.9808 mL | 4.9039 mL | 9.8078 mL | |
| 5 mM | 0.1962 mL | 0.9808 mL | 1.9616 mL | |
| 10 mM | 0.0981 mL | 0.4904 mL | 0.9808 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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