| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
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| Targets |
The primary target of MC-Val-Cit-PAB-indibulin, 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, indibulin, is an orally applicable inhibitor of tubulin assembly. Upon binding of the ADC to the target antigen, the conjugate is internalized, and the linker is cleaved to release indibulin, which then inhibits tubulin polymerization, leading to mitotic arrest and 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-indibulin 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. Indibulin is an orally active inhibitor of tubulin assembly, and its targeted delivery via the ADC linker is designed to improve its therapeutic index. The compound's stability in plasma and its ability to release indibulin upon internalization are also evaluated.
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| ln Vivo |
In vivo studies of MC-Val-Cit-PAB-indibulin are focused on evaluating the antitumor efficacy and pharmacokinetics of ADCs constructed with this drug-linker conjugate. The compound is used to build ADCs with potent antitumor activity. In xenograft models, ADCs containing MC-Val-Cit-PAB-indibulin are expected to show potent antitumor activity with improved pharmacokinetics and a better therapeutic index compared to unconjugated indibulin. The targeted delivery of indibulin via the ADC is designed to enhance efficacy and reduce systemic 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-indibulin 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 indibulin 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 indibulin 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-indibulin 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. Indibulin is a tubulin assembly inhibitor, and its effects on the cell cycle can be assessed by flow cytometry. Internalization and release of indibulin can be assessed using fluorescently labeled antibodies or by measuring free indibulin in cell lysates.
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| Animal Protocol |
For in vivo animal experiments, MC-Val-Cit-PAB-indibulin 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 indibulin 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 indibulin 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-indibulin as a drug-linker conjugate are designed to improve the pharmacokinetics of the indibulin 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 indibulin 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-indibulin 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 potency of indibulin, and the stability of the linker. Indibulin is an inhibitor of tubulin assembly, and off-target release could cause toxicity similar to other tubulin-binding agents, including myelosuppression and neuropathy. 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-indibulin 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 orally active tubulin assembly inhibitor indibulin with the MC-Val-Cit-PAB ADC linker. It is an antibody-conjugated active molecule and exhibits potent antitumor activity.
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| Molecular Formula |
C50H55CLN9O8
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|---|---|
| Molecular Weight |
945.480210542679
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| Exact Mass |
944.386
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| CAS # |
2055896-95-0
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| PubChem CID |
139035084
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| Appearance |
Light yellow to brown solid powder
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
68
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| Complexity |
1770
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(C1=CN(CC2C=CC(Cl)=CC=2)C2=CC=CC=C12)(=O)C(=O)NC1=CC=[N+](CC2C=CC(NC(=O)[C@H](CCCNC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN3C(C=CC3=O)=O)=CC=2)C=C1
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| InChi Key |
QLPCKALAMKCOEG-FQDNZFBXSA-O
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| InChi Code |
InChI=1S/C50H54ClN9O8/c1-32(2)45(57-42(61)12-4-3-7-26-60-43(62)21-22-44(60)63)48(66)56-40(10-8-25-53-50(52)68)47(65)54-36-19-15-33(16-20-36)29-58-27-23-37(24-28-58)55-49(67)46(64)39-31-59(41-11-6-5-9-38(39)41)30-34-13-17-35(51)18-14-34/h5-6,9,11,13-24,27-28,31-32,40,45H,3-4,7-8,10,12,25-26,29-30H2,1-2H3,(H6,52,53,54,56,57,61,65,66,68)/p+1/t40-,45-/m0/s1
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| Chemical Name |
N-[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-[[4-[[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]amino]pyridin-1-ium-1-yl]methyl]anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide
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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, 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 : ~125 mg/mL (~132.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (2.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 22.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0577 mL | 5.2883 mL | 10.5766 mL | |
| 5 mM | 0.2115 mL | 1.0577 mL | 2.1153 mL | |
| 10 mM | 0.1058 mL | 0.5288 mL | 1.0577 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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