| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
This compound is a linker molecule rather than a therapeutic agent with a pharmacological target. It serves as a conjugation reagent for ADC development. The maleimide group targets thiol groups on antibodies for stable conjugation. The Val-Cit peptide is cleavable by cathepsin B, an enzyme overexpressed in tumor cells, enabling controlled payload release.
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|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
In vitro, the linker itself does not exhibit biological activity. Its activity is assessed indirectly through the efficacy of the ADC conjugates it helps create. The Val-Cit dipeptide is specifically cleaved by cathepsin B in the lysosomal compartment of target cells, releasing the attached payload. The PEG spacer improves solubility and reduces aggregation of ADC conjugates. |
| ln Vivo |
In vivo, the linker enables targeted delivery of cytotoxic payloads to tumor cells through ADC conjugation. After the ADC binds to its target antigen and is internalized, the Val-Cit linker is cleaved by cathepsin B, releasing the payload specifically within the tumor cell. This reduces systemic toxicity compared to unconjugated payloads.
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| Enzyme Assay |
Non-cellular assays for this linker include stability testing in various buffers and biological media. The Val-Cit dipeptide's susceptibility to enzymatic cleavage can be assessed by incubating the linker with cathepsin B and measuring release of the PNP group or a model payload by HPLC or LC-MS. Maleimide reactivity with thiol-containing compounds can be monitored by UV-Vis or mass spectrometry.
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| Cell Assay |
In vitro cellular experiments involve conjugating the linker to a cytotoxic payload and an antibody to form an ADC. The ADC is then tested in cell-based assays for target binding, internalization, and cytotoxicity against antigen-positive cancer cells. Cathepsin B-dependent payload release can be confirmed by comparing cytotoxicity in cells with and without cathepsin B inhibition.
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| Animal Protocol |
In vivo animal studies use ADC conjugates prepared with this linker. Tumor xenograft models in mice are treated with the ADC, and antitumor efficacy is assessed by tumor volume measurements. Pharmacokinetics, biodistribution, and toxicity are evaluated to determine the therapeutic index. The linker's cleavability contributes to improved efficacy and reduced off-target toxicity.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are determined for the complete ADC rather than the linker alone. The PEG moiety improves solubility and circulation half-life of the ADC. The Val-Cit linker is designed for stability in circulation and rapid cleavage upon internalization into target cells. The linker itself is not administered as a therapeutic agent.
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| Toxicity/Toxicokinetics |
The linker is a chemical reagent and is not typically evaluated for standalone toxicity. Toxicity is assessed for the final ADC conjugate in preclinical studies. The Val-Cit-PAB system is designed to minimize systemic toxicity by enabling targeted payload release. The compound should be handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
Mal-amido-PEG2-Val-Cit-PAB-PNP is a cleavable ADC linker containing a Val-Cit dipeptide that is specifically cleaved by cathepsin B. The maleimide group enables site-specific conjugation to antibodies, while the PNP group is a leaving group for payload attachment. The PEG spacer improves solubility. This product is for research purposes only and is not for human therapeutic use.
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| Molecular Formula |
C39H50N8O14
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|---|---|
| Molecular Weight |
854.859509944916
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| Exact Mass |
854.344
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| CAS # |
2112738-13-1
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| PubChem CID |
129009582
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| Appearance |
White to off-white solid powder
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| LogP |
0.3
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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 |
27
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| Heavy Atom Count |
61
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| Complexity |
1520
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C([C@H](C(C)C)NC(CCOCCOCCNC(CCN1C(C=CC1=O)=O)=O)=O)N[C@H](C(NC1C=CC(COC(=O)OC2C=CC(=CC=2)[N+](=O)[O-])=CC=1)=O)CCCNC(N)=O
|
| InChi Key |
PAGAOQLHMRBQFV-QGRQJHSQSA-N
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| InChi Code |
InChI=1S/C39H50N8O14/c1-25(2)35(45-32(49)16-20-58-22-23-59-21-18-41-31(48)15-19-46-33(50)13-14-34(46)51)37(53)44-30(4-3-17-42-38(40)54)36(52)43-27-7-5-26(6-8-27)24-60-39(55)61-29-11-9-28(10-12-29)47(56)57/h5-14,25,30,35H,3-4,15-24H2,1-2H3,(H,41,48)(H,43,52)(H,44,53)(H,45,49)(H3,40,42,54)/t30-,35-/m0/s1
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| Chemical Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[3-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate
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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 Vitro) |
DMSO : ~250 mg/mL (~292.45 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1698 mL | 5.8489 mL | 11.6978 mL | |
| 5 mM | 0.2340 mL | 1.1698 mL | 2.3396 mL | |
| 10 mM | 0.1170 mL | 0.5849 mL | 1.1698 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.
Products are for research use only; We do not sell to patients
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