| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MC-VA-PABC-MMAE targets intracellular cathepsin B. Upon ADC internalization into cancer cells, the VA dipeptide is cleaved by cathepsin B in lysosomes, releasing the active MMAE payload, which then targets and inhibits tubulin polymerization, leading to G2/M cell cycle arrest and apoptosis.
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|---|---|
| ln Vitro |
The ADC is made up of a preamp to which the ADC input connects the ADC cytotoxin [1].
In cell-free cathepsin B cleavage assays, the VA dipeptide is efficiently cleaved, releasing free MMAE. The released MMAE shows potent cytotoxicity against various cancer cell lines (IC50 in low nM range) by inhibiting tubulin polymerization and disrupting the cellular microtubule network. |
| ln Vivo |
In vivo efficacy is observed in mouse xenograft models when MC-VA-PABC-MMAE is conjugated to tumor-targeting antibodies. The ADC accumulates in tumors, internalizes, and releases MMAE, resulting in potent tumor growth inhibition at well-tolerated doses. Detailed PK/Tox follows the conjugated ADC.
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| Enzyme Assay |
The cathepsin B cleavage assay is performed using recombinant human cathepsin B. The MC-VA-PABC-MMAE conjugate is incubated with cathepsin B in cleavage buffer (pH 5.5) at 37degC for 1-4 hours. The released MMAE is quantified by LC-MS/MS to evaluate linker stability and cleavage efficiency.
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| Cell Assay |
For in vitro cytotoxicity, antigen-positive cancer cells are treated with an ADC containing this linker-payload. Cells are incubated for 96-120 hours. Cell viability is measured using CellTiter-Glo. Cathepsin B inhibition or competition with free MMAE can confirm the on-target mechanism of the released payload.
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| Animal Protocol |
Animal protocols depend on the specific ADC. Typically, mice bearing xenografts of target antigen-positive tumors receive the ADC intravenously at 1-10 mg/kg, once weekly for 2-3 weeks. Tumor volume and body weight are monitored. Blood samples are collected for PK analysis.
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| ADME/Pharmacokinetics |
TK of MC-VA-PABC-MMAE is typically studied as part of an ADC. After injection, the ADC shows biphasic elimination: a rapid distribution phase followed by a slow elimination phase (half-life of days in humans). The linker-payload is stable in circulation, with minimal premature release.
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| Toxicity/Toxicokinetics |
Standard ADC safety precautions apply. Toxicity is context-dependent. The free MMAE payload can cause peripheral neuropathy, neutropenia, and other off-target toxicities at high doses. In ADC form, toxicity is reduced but requires monitoring. Not for human therapeutic use.
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| References |
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| Additional Infomation |
This is a research-grade ADC linker-payload. It is incorporated into commercially approved ADCs (e.g., brentuximab vedotin, polatuzumab vedotin) where the valine-citrulline (VC) dipeptide is used. The sequence is maleimidocaproyl-valine-alanine-PABC-MMAE. Molecular weight: approx. 1385.68.
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| Molecular Formula |
C65H99N9O14
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|---|---|
| Molecular Weight |
1230.53
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| Exact Mass |
1229.731
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| CAS # |
1818864-51-5
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| PubChem CID |
164886612
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| Appearance |
White to off-white solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
35
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| Heavy Atom Count |
88
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| Complexity |
2340
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| Defined Atom Stereocenter Count |
12
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| SMILES |
[C@@H](C(=O)N[C@H](C(=O)NC1=CC=C(C=C1)COC(N([C@H](C(N[C@@H](C(C)C)C(=O)N([C@@]([H])([C@@H](C)CC)[C@@H](CC(=O)N1[C@]([H])([C@@H]([C@@H](C)C(=O)N[C@H](C)[C@@H](O)C2=CC=CC=C2)OC)CCC1)OC)C)=O)C(C)C)C)=O)C)(C(C)C)NC(CCCCCN1C(=O)C=CC1=O)=O
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| InChi Key |
IQZWSFIVBFLXDH-RKMHKBIWSA-N
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| InChi Code |
InChI=1S/C65H99N9O14/c1-16-41(8)57(49(86-14)36-53(78)73-35-23-26-48(73)59(87-15)42(9)60(80)66-43(10)58(79)46-24-19-17-20-25-46)71(12)64(84)55(39(4)5)70-63(83)56(40(6)7)72(13)65(85)88-37-45-28-30-47(31-29-45)68-61(81)44(11)67-62(82)54(38(2)3)69-50(75)27-21-18-22-34-74-51(76)32-33-52(74)77/h17,19-20,24-25,28-33,38-44,48-49,54-59,79H,16,18,21-23,26-27,34-37H2,1-15H3,(H,66,80)(H,67,82)(H,68,81)(H,69,75)(H,70,83)/t41-,42+,43+,44-,48-,49+,54-,55-,56-,57-,58+,59+/m0/s1
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| Chemical Name |
[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate
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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 and light. |
| 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 (~81.27 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.03 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 25.0 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: ≥ 2.5 mg/mL (2.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8127 mL | 4.0633 mL | 8.1266 mL | |
| 5 mM | 0.1625 mL | 0.8127 mL | 1.6253 mL | |
| 10 mM | 0.0813 mL | 0.4063 mL | 0.8127 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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