| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
MC-Gly-Gly-Phe-Gly-PAB-MMAE targets tubulin through its MMAE payload. MMAE is a highly potent antimitotic agent that inhibits tubulin polymerization, leading to cell-cycle arrest at the G2/M phase and subsequent apoptosis. The MC-Gly-Gly-Phe-Gly-PAB linker is a cleavable peptide-based linker designed for ADC applications. The linker is stable in systemic circulation but is cleaved by cathepsin B and other lysosomal proteases after ADC internalization into target cells, releasing the MMAE payload. As a control, this conjugate does not include the targeting antibody component.
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| ln Vitro |
In vitro, MC-Gly-Gly-Phe-Gly-PAB-MMAE serves as a control for ADC studies. The free MMAE payload, when released from the linker by proteolytic cleavage, inhibits tubulin polymerization with high potency (IC50 in low nanomolar range). The conjugate itself, without antibody-mediated targeting, may have minimal cellular uptake and cytotoxicity in non-phagocytic cells. In ADC control experiments, this conjugate is used to validate that the observed anti-proliferative activity of a complete ADC is dependent on antibody-mediated targeting rather than non-specific release of payload. The compound is used in tumor research for control experiments.
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| ln Vivo |
No direct in vivo activity studies have been published for MC-Gly-Gly-Phe-Gly-PAB-MMAE as a standalone conjugate. In ADC studies, the complete ADC containing this linker-payload conjugate shows potent anti-tumor activity in xenograft mouse models. The MMAE payload, when released in tumor tissue, induces potent anti-mitotic effects leading to tumor regression. The control conjugate without antibody is expected to have limited in vivo activity due to rapid clearance and lack of tumor targeting. It is primarily used as a negative control in ADC pharmacology studies to confirm target-dependent activity.
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| Enzyme Assay |
No specific enzyme/receptor binding protocols have been established for MC-Gly-Gly-Phe-Gly-PAB-MMAE as it is a linker-drug conjugate rather than a direct ligand. For cathepsin B cleavage assays, the conjugate is incubated with recombinant cathepsin B in assay buffer (pH 5.5) at 37degC for 1-24 hours. Cleavage products are analyzed by LC-MS to confirm release of MMAE. For tubulin binding assays, standard protocols involve incubating purified tubulin with varying concentrations of MMAE or the released payload, and measuring tubulin polymerization by turbidity at 340 nm. The conjugate itself does not bind tubulin directly until the linker is cleaved.
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| Cell Assay |
In vitro cellular protocols for MC-Gly-Gly-Phe-Gly-PAB-MMAE as an ADC control involve culturing cancer cell lines (e.g., HER2-positive breast cancer cells or other target antigen-expressing cells) in RPMI-1640 or DMEM with 10% FBS at 37degC in 5% CO2. Cells are seeded in 96-well plates at 5,000-10,000 cells/well. For comparison, cells are treated with varying concentrations of complete ADC (0.01-100 nM) and with the control conjugate (MC-Gly-Gly-Phe-Gly-PAB-MMAE alone) in parallel. Cell viability is assessed after 72-96 hours using CellTiter-Glo or MTT assays. Lack of cytotoxicity with the control conjugate confirms that the ADC's activity is mediated by antibody-targeted delivery. For internalization studies, control conjugate and ADC are compared. All experiments are performed in triplicate.
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| Animal Protocol |
For in vivo studies using MC-Gly-Gly-Phe-Gly-PAB-MMAE as an ADC control, standard protocols involve xenograft models in immunodeficient mice (nude or NSG mice, 6-8 weeks old). Approximately 5×10⁶ target antigen-positive cancer cells are injected subcutaneously. When tumors reach ~150-200 mm3, mice are randomized into treatment groups (n=5-10 per group). Groups include vehicle, complete ADC (1-10 mg/kg), and control conjugate (at equivalent payload dose). Conjugate is administered intravenously. Tumor volumes are measured every 2-3 days using digital calipers. Body weights are monitored for toxicity. Control conjugate should show minimal anti-tumor activity compared to complete ADC, confirming target-dependence. All procedures approved by institutional animal care committees.
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| ADME/Pharmacokinetics |
No direct pharmacokinetic studies have been published for MC-Gly-Gly-Phe-Gly-PAB-MMAE. The compound is soluble in DMSO (~130 mg/mL) and has limited water solubility (<0.1 mg/mL). For in vivo formulation, a suspension formulation of 3.25 mg/mL in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline is recommended. The pharmacokinetic properties of the conjugate are determined by the linker-payload structure, with peptide-based linkers designed for stability in circulation (half-life typically hours to days) and cleavage within lysosomes after internalization. The MMAE payload has a reported half-life of approximately 1-3 hours when administered free, but significantly longer when conjugated. No specific PK parameters are reported for this control conjugate.
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| Toxicity/Toxicokinetics |
According to safety data sheets, MC-Gly-Gly-Phe-Gly-PAB-MMAE is for research use only. MMAE is a highly potent antimitotic agent with potential toxicity if released inappropriately. Extreme caution must be exercised when handling this compound. Standard laboratory safety precautions should be followed: wear protective gloves, safety goggles, and a lab coat. Work in a well-ventilated fume hood. Avoid inhalation, ingestion, and contact with skin and eyes. The compound should be stored as a powder at -20degC for up to 3 years or at 4degC for 2 years. In solution, store at -80degC for 6 months or -20degC for 1 month. Note that this product is not stable in solution; use freshly prepared working solution for optimal results. This product is not for human therapeutic use.
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| References | |
| Additional Infomation |
MC-Gly-Gly-Phe-Gly-PAB-MMAE is a linker-drug conjugate used as a control for antibody-drug conjugates (ADCs) in tumor research. The conjugate consists of a cleavable peptide-based linker (MC-Gly-Gly-Phe-Gly-PAB) and the potent antimitotic agent monomethyl auristatin E (MMAE). MMAE is a synthetic derivative of the natural product dolastatin 10 and is a highly potent tubulin inhibitor. The MC (maleimidocaproyl) group allows conjugation to cysteine residues of antibodies. The PAB (para-aminobenzyl) group is a self-immolative spacer that facilitates efficient release of MMAE after proteolytic cleavage of the peptide linker by cathepsin B in lysosomes. This control conjugate is used to validate target-dependent ADC activity in vitro and in vivo. No clinical trial data is available; the compound is for research use only and not approved for human therapy.
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| Molecular Formula |
C72H103N11O16
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|---|---|
| Molecular Weight |
1378.65
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| CAS # |
3055607-13-8
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| Appearance |
White to off-white solid powder
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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: 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 (~94.30 mM; with sonication)
H2O : ~< 0.1 mg/mL (insoluble) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.25 mg/mL (2.36 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one)),suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of clear DMSO stock solution (32.5 mg/mL) was added to 400 μL of PEG300 and mixed thoroughly. Then, 50 μL of Tween-80 was added to the above system and mixed thoroughly. Finally, 450 μL of physiological saline was added to bring the volume to 1 mL. Preparation of physiological saline: 0.9 g of sodium chloride was dissolved in ddH₂O and brought to a volume of 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 3.25 mg/mL (2.36 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 sonication. For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 32.5 mg/mL clear DMSO stock solution was added to 900 μL of 20% SBE-β-CD physiological saline solution and mixed thoroughly. 2 g of SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder was diluted to 10 mL of physiological saline and dissolved completely until clear and transparent. 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: ≥ 3.25 mg/mL (2.36 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 | 0.7253 mL | 3.6267 mL | 7.2535 mL | |
| 5 mM | 0.1451 mL | 0.7253 mL | 1.4507 mL | |
| 10 mM | 0.0725 mL | 0.3627 mL | 0.7253 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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