Mc-Val-Cit-PABC-PNP (Synonyms: Maleimidocaproyl-LValine-LCitrullinep-Aminobenzyl Alcohol pNitrophenyl Carbonate) |
رقم الكتالوجGC17032
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إن Mc-Val-Cit-PABC-PNP عبارة عن رابط ADC قابل للانقسام من نوع cathepsinيمكن استخدام Mc-Val-Cit-PABC-PNP في تخليق اتحادات الأدوية والأجسام المضادة (ADCs)
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 159857-81-5
Sample solution is provided at 25 µL, 10mM.
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Mc-Val-Cit-PABC-PNP is a cathepsin-cleavable peptide linker for Antibody-Drug Conjugates (ADCs). Mc-Val-Cit-PABC-PNP acts as a substrate for lysosomal proteases (such as cathepsin B) via its valine-citrulline dipeptide sequence. Upon enzymatic cleavage in the tumor microenvironment, Mc-Val-Cit-PABC-PNP releases the drug payload, while enabling precise drug release control through a self-immolative spacer. Mc-Val-Cit-PABC-PNP can be used in the synthesis of antibody-drug conjugates and related cancer therapy research[1-4].
References:
[1] Bisbal Lopez L, Ravazza D, Bocci M, et al. Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker. Front Pharmacol. 2023 Dec 6;14:1320524.
[2] Che-Leung Law, Julie McEarchern, Jonathan Drachman. Anti-cd70 antibody-drug conjugates and their use for the treatment of cancer and immune disorders. Patent WO2005081711A2.
[3] James P. Basilion, Xinning Wang, Natalie Walker. Psma targeted conjugate compounds and uses thereof. Patent. US20250222122A1.
[4] Fumiyoshi Okano, Takanori Saito. Conjugate of caprin-1 antibody linked to immune activator for cancer treatment. Patent. US20250249092A1.
Application of Mc-Val-Cit-PABC-PNP in Conjugation with a Monoclonal Antibody[1]
This protocol is adapted from research data and provided for reference only. Adjustments may be necessary based on specific experimental requirements.
1. Reagent Preparation: Prepare a PBS solution of the monoclonal antibody (e.g., Bevacizumab; 25mg/ml). Prepare a TECP (Tris(2-carboxyethyl)phosphine; 2mg/ml) solution for antibody reduction. Prepare a solution of Mc-Val-Cit-PABC-PNP. Prepare an N-acetylcysteine (NAC; 2mg/ml) solution for reaction quenching. Prepare dialysis tubing (molecular weight cut-off: 3000Da) and PBS buffer (pH=7.4).
2. Linker-Drug Conjugate (Vedotin) Synthesis: Weigh 28.00mg of Mc-Val-Cit-PABC-PNP and dissolve in 0.5ml of DMF. Add 18.15mg of MMAE to this solution, followed by 12.01mg of pyridine. Stir the reaction at room temperature for 16 hours. After completion, purify the crude product using preparative reverse-phase high-performance liquid chromatography (rp-HPLC), collecting the target main peak fraction. Lyophilize the collected solution to obtain the final product, Mc-Val-Cit-PABC-PNP-MMAE (Vedotin).
3. Antibody Reduction: To a 1ml PBS reaction system containing 100µL of monoclonal antibody (25mg/ml), add 7.2µL of TECP solution (2mg/ml). Stir the reaction at 25°C for 2 hours to expose the free thiol groups of the antibody.
4. Linker-Drug Conjugate Coupling: To the above reduced antibody reaction system, add 56µL of the Mc-Val-Cit-PABC-PNP-MMAE solution in DMAC (8mg/ml). Continue the reaction at 25°C for 50 minutes.
5. Reaction Quenching and Purification: Add an excess of NAC solution (2mg/ml; 14µL) to the reaction system and stir at 25°C for 30 minutes to quench any unreacted maleimide groups. Transfer the reaction solution to dialysis tubing and dialyze against PBS (pH=7.4; 500ml) at 4°C for 24 hours. After dialysis, lyophilize the product and store it at -80°C for later use.
Precautions:
(1) The entire conjugation operation should be performed under controlled temperature, and light-sensitive reagents should be protected from light.
(2) For your safety and health, please wear a lab coat and disposable gloves during operation.
References:
[1] Li Y, Si R, Wang J, et al. Discovery of novel antibody-drug conjugates bearing tissue protease specific linker with both anti-angiogenic and strong cytotoxic effects. Bioorg Chem. 2023 Aug;137:106575.
| Cas No. | 159857-81-5 | SDF | |
| المرادفات | Maleimidocaproyl-LValine-LCitrullinep-Aminobenzyl Alcohol pNitrophenyl Carbonate | ||
| Chemical Name | (Z)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S,Z)-1-hydroxy-1-(((S)-5-((hydroxy(imino)methyl)amino)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxopentan-2-yl)imino)-3-methylbutan-2-yl)hexanimidic acid | ||
| Canonical SMILES | CC([C@@](/N=C(O)/CCCCCN1C(C=CC1=O)=O)([H])/C(O)=N/[C@@](C(NC2=CC=C(COC(OC3=CC=C(N(=O)=O)C=C3)=O)C=C2)=O)([H])CCCNC(O)=N)C | ||
| Formula | C35H43N7O11 | M.Wt | 737.76 |
| الذوبان | ≥ 36.9mg/mL in DMSO | Storage | 4°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3555 mL | 6.7773 mL | 13.5545 mL |
| 5 mM | 271.1 μL | 1.3555 mL | 2.7109 mL |
| 10 mM | 135.5 μL | 677.7 μL | 1.3555 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)