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| Other Sizes |
| Targets |
The primary application of Modified MC-VC-PABC is as a linker component in antibody-drug conjugates (ADCs), where it serves to covalently attach cytotoxic drug payloads to targeting antibodies. While not a traditional pharmacological target, the molecule itself is designed to be stable and non-cleavable within the biological environment, ensuring that the attached cytotoxic payload remains conjugated to the antibody until the ADC is internalized by target cells. The DNA alkylating agent DUBA, which is linked via this ADC linker, is the active cytotoxic moiety that ultimately exerts the therapeutic effect by damaging DNA in cancer cells. The linker's stability and non-cleavable nature are critical properties that influence the pharmacokinetics, efficacy, and safety profile of the resulting ADC construct.
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| ln Vitro |
In vitro activity of Modified MC-VC-PABC is evaluated indirectly through the characterization of the complete ADC construct in which it is incorporated. The linker itself does not possess intrinsic pharmacological activity but enables the targeted delivery of the DUBA payload to cancer cells. In cell-based assays, ADCs containing Modified MC-VC-PABC are tested for their ability to bind to target antigens on cancer cell surfaces, undergo receptor-mediated internalization, and release the cytotoxic payload intracellularly. The potency of these ADCs is typically measured by their half-maximal inhibitory concentration (IC50) in cancer cell proliferation assays, comparing the activity of the ADC to the free payload and unconjugated antibody controls. The non-cleavable nature of the linker ensures that the payload remains attached even after internalization, leading to sustained cytotoxic activity within the target cell.
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| ln Vivo |
In vivo activity of Modified MC-VC-PABC is assessed through studies of ADC constructs incorporating this linker in animal models of human cancer. Tumor-bearing mice (typically xenograft models) are administered the ADC at various dose levels, and antitumor efficacy is evaluated by measuring tumor volume reduction over time compared to vehicle and control groups. Pharmacokinetic studies in rodents determine the stability, half-life, and tissue distribution of the ADC, which are influenced by the linker's properties. The non-cleavable nature of the linker contributes to improved stability in circulation, potentially reducing premature payload release and off-target toxicity. Efficacy is typically expressed as tumor growth inhibition (TGI) percentage or as the dose required to achieve tumor stasis or regression. Safety is monitored through body weight changes and clinical observations.
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| Enzyme Assay |
In vitro enzyme/receptor binding (cell-free) assays are not directly applicable to Modified MC-VC-PABC as it is a linker molecule rather than a traditional enzyme inhibitor or receptor ligand. However, the properties of the linker can be characterized using biochemical methods to confirm its structure and purity. High-performance liquid chromatography (HPLC) and mass spectrometry are used to verify the molecular weight (1331.81 g/mol) and chemical composition (C65H75ClN12O17). The stability of the linker in various buffer systems and plasma can be assessed by incubating the compound in relevant media and monitoring degradation over time using analytical techniques. Additionally, the ability of the linker to conjugate to antibodies and payloads can be evaluated through conjugation efficiency assays, typically measured by UV-Vis spectroscopy or size-exclusion chromatography.
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| Cell Assay |
In vitro cellular assays for Modified MC-VC-PABC are typically performed using the complete ADC construct rather than the linker alone. Cancer cell lines expressing the target antigen are cultured in appropriate media and treated with varying concentrations of the ADC. Following incubation, cell viability is measured using standard assays such as MTT, CellTiter-Glo, or resazurin reduction. The IC50 values are calculated from dose-response curves to determine the potency of the ADC. Antigen binding and internalization are assessed using flow cytometry or immunofluorescence microscopy, typically employing fluorescently labeled secondary antibodies. The mechanism of cell death (apoptosis vs. necrosis) can be investigated using annexin V/propidium iodide staining or caspase activity assays. Cytotoxicity is compared between target antigen-positive and antigen-negative cell lines to confirm target specificity.
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| Animal Protocol |
In vivo animal studies for Modified MC-VC-PABC are conducted using immunodeficient mice bearing human tumor xenografts. Typically, 6-8 week old female athymic nude mice or NSG mice are implanted subcutaneously with cancer cells expressing the target antigen. Once tumors reach a predetermined size (e.g., 100-200 mm3), animals are randomized into treatment groups and administered the ADC construct via intravenous injection at various doses and schedules. Tumor size is measured twice weekly using calipers, and body weight is monitored as a safety indicator. At study termination, tumors are excised, weighed, and processed for histopathological analysis or biomarker assessment. Pharmacokinetic samples are collected at multiple time points to determine ADC stability and exposure in circulation. Efficacy is expressed as tumor growth inhibition (TGI) relative to vehicle control.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Modified MC-VC-PABC are characterized as part of the ADC construct rather than the isolated linker. The linker's non-cleavable nature contributes to the overall stability of the ADC in circulation, resulting in a longer half-life and reduced premature payload release compared to cleavable linkers. The ADC typically exhibits biphasic elimination, with an initial distribution phase followed by a slower elimination phase. The volume of distribution is generally limited to the vascular compartment due to the large molecular weight of the ADC construct. Clearance occurs primarily through proteolytic degradation and elimination of small peptide fragments. The linker's hydrophobicity can influence aggregation and pharmacokinetic behavior, which is typically assessed by size-exclusion chromatography and hydrophobic interaction chromatography during ADC development. The oral bioavailability is not applicable as ADCs are administered parenterally.
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| Toxicity/Toxicokinetics |
Toxicological properties of Modified MC-VC-PABC are evaluated as part of the complete ADC construct in preclinical safety studies. The linker itself is not expected to be directly toxic, but it influences the toxicity profile of the ADC through its impact on stability, pharmacokinetics, and payload release. Standard toxicology studies are conducted in relevant animal species (typically rodents and non-human primates) to assess the safety of the ADC. Parameters evaluated include clinical observations, body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathology. The non-cleavable nature of the linker may reduce off-target toxicity by minimizing premature release of the DUBA payload in circulation. However, on-target toxicity can still occur due to antigen expression on normal tissues. The compound is for research use only and has not undergone clinical toxicology testing.
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| References | |
| Additional Infomation |
Modified MC-VC-PABC is a specialized research tool used exclusively for the development of antibody-drug conjugates (ADCs). As a non-cleavable ADC linker, it is designed to provide stable conjugation between the targeting antibody and the cytotoxic payload (DUBA, a DNA alkylating agent), ensuring that the payload remains attached until the ADC is internalized by the target cell. The molecule has a molecular formula of C65H75ClN12O17 and a molecular weight of approximately 1331.81 g/mol. It is not a therapeutic agent itself but is a key component in the construction of next-generation ADC therapeutics. 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. Its modification from the standard MC-VC-PABC structure provides unique properties that may be advantageous for specific ADC applications.
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| Molecular Formula |
C65H75CLN12O17
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|---|---|
| Molecular Weight |
1331.81421494484
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| Exact Mass |
1330.506
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| CAS # |
1345681-58-4
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| PubChem CID |
88899540
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
34
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| Heavy Atom Count |
95
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| Complexity |
2630
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| Defined Atom Stereocenter Count |
3
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| SMILES |
ClC[C@@H]1CN(C(C2=CN3C=C(C=CC3=N2)NC(C2C=CC(=CC=2)O)=O)=O)C2C=C(C3C=CC=C(C)C=3C1=2)OC(N(CCOCCO)CCN(C(=O)OCC1C=CC(=CC=1)NC([C@H](CCCNC(N)=O)NC([C@H](C(C)C)NC(=O)OCCOCCN1C(C=CC1=O)=O)=O)=O)C)=O
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| InChi Key |
RFQYSAASDBNNDZ-UCGHAGIGSA-N
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| InChi Code |
InChI=1S/C65H75ClN12O17/c1-39(2)57(73-63(88)93-32-31-92-29-26-77-53(81)20-21-54(77)82)60(85)72-48(9-6-22-68-62(67)87)59(84)69-44-14-10-41(11-15-44)38-94-64(89)74(4)23-24-75(25-28-91-30-27-79)65(90)95-51-33-50-56(55-40(3)7-5-8-47(51)55)43(34-66)35-78(50)61(86)49-37-76-36-45(16-19-52(76)71-49)70-58(83)42-12-17-46(80)18-13-42/h5,7-8,10-21,33,36-37,39,43,48,57,79-80H,6,9,22-32,34-35,38H2,1-4H3,(H,69,84)(H,70,83)(H,72,85)(H,73,88)(H3,67,68,87)/t43-,48+,57+/m1/s1
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| Chemical Name |
[(1S)-1-(chloromethyl)-3-[6-[(4-hydroxybenzoyl)amino]imidazo[1,2-a]pyridine-2-carbonyl]-9-methyl-1,2-dihydrobenzo[e]indol-5-yl] N-[2-[[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethoxycarbonylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methoxycarbonyl-methylamino]ethyl]-N-[2-(2-hydroxyethoxy)ethyl]carbamate
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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 : ~146.67 mg/mL (~110.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.44 mg/mL (1.83 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 24.4 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: 2.44 mg/mL (1.83 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 24.4 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. View More
Solubility in Formulation 3: ≥ 2.44 mg/mL (1.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7509 mL | 3.7543 mL | 7.5086 mL | |
| 5 mM | 0.1502 mL | 0.7509 mL | 1.5017 mL | |
| 10 mM | 0.0751 mL | 0.3754 mL | 0.7509 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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