| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Mal-PEG8-Val-Cit-PAB-MMAF targets tubulin via the MMAF payload. MMAF is a potent auristatin derivative that inhibits tubulin polymerization, thereby blocking cell division and inducing mitotic arrest. The Val-Cit-PAB linker is designed for cathepsin-mediated cleavage, ensuring selective payload release within cancer cell lysosomes.
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| ln Vitro |
Not available. MMAF potently inhibits tubulin polymerization and exhibits cytotoxicity in various cancer cell lines, typically with IC50 values in the low nanomolar range. Upon release from the ADC following cleavage of the Val-Cit linker, free MMAF enters target cells and binds to tubulin, disrupting microtubule dynamics and inducing G2/M cell cycle arrest and apoptosis.
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| ln Vivo |
Not available. When incorporated into an ADC conjugate, Mal-PEG8-Val-Cit-PAB-MMAF delivers MMAF selectively to antigen-positive tumor cells. In mouse xenograft models, MMAF-based ADCs exhibit potent anti-tumor activity, inducing tumor regression and prolonged survival at doses typically ranging from 1-10 mg/kg administered intravenously.
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| Enzyme Assay |
Not available. Standard cathepsin cleavage assays involve incubating the linker-MMAF conjugate (1-50 uM) with recombinant cathepsin B (10-100 nM) in 50 mM sodium acetate buffer (pH 5.0) containing 2 mM DTT and 1 mM EDTA at 37degC for 2-24 hours, followed by HPLC-MS analysis to quantify MMAF release. Maleimide conjugation efficiency is assessed by thiol titration.
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| Cell Assay |
Standard cytotoxicity assays involve treating antigen-positive cancer cells with Mal-PEG8-Val-Cit-PAB-MMAF-conjugated ADCs (0.001-100 nM) for 72-120 hours, then assessing viability using MTT, CellTiter-Glo, or clonogenic assays. The Val-Cit linker requires lysosomal proteases for cleavage, so activity is typically observed only after ADC internalization.
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| Animal Protocol |
Not available. For in vivo efficacy studies, standard protocols involve intravenous administration of the ADC conjugate (1-20 mg/kg, single dose or q7d × 2-4 doses) in mice bearing established subcutaneous tumor xenografts, monitoring tumor volume and body weight every 2-3 days for 3-6 weeks, with PK sampling at various time points for plasma concentration analysis.
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| ADME/Pharmacokinetics |
Not available. The PEG8 spacer improves aqueous solubility and reduces aggregation of the ADC conjugate. The Val-Cit linker provides excellent serum stability (half-life typically days) while allowing efficient cleavage by cathepsins in lysosomes (within hours of internalization). ADC pharmacokinetics are primarily determined by the antibody.
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| Toxicity/Toxicokinetics |
Toxicity associated with MMAF-based ADCs includes neutropenia, thrombocytopenia, peripheral neuropathy, and hepatotoxicity due to off-target payload release. The Val-Cit linker reduces systemic toxicity compared to non-cleavable linkers. Specific data for this conjugate are not available.
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| References | |
| Additional Infomation |
Mal-PEG8-Val-Cit-PAB-MMAF is a research-grade drug-linker conjugate for ADC development. MMAF-based ADCs such as belantamab mafodotin have received regulatory approval for multiple myeloma, demonstrating the clinical utility of this linker-payload platform. This specific conjugate is for laboratory research and has not been individually approved for clinical use.
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| Molecular Formula |
C81H129N11O24
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|---|---|
| Molecular Weight |
1640.95
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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 |
| 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6094 mL | 3.0470 mL | 6.0940 mL | |
| 5 mM | 0.1219 mL | 0.6094 mL | 1.2188 mL | |
| 10 mM | 0.0609 mL | 0.3047 mL | 0.6094 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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