Name: Mc-Val-Cit-PABC-PNP
Brand: BOC Sciences
Price: 298 USD
Availability: MadeToOrder

Synonyms

[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonateMc-Val-Cit-PABC-PNP159857-81-5MC-Val-Cit-PAB-PNPSCHEMBL3205376HYSPJPGXSALJRR-DHIFEGFHSA-NC3

IUPAC Name

Canonical SMILES

CC(C)C(C(=O)NC(CCCNC(=O)N)C(=O)NC1=CC=C(C=C1)COC(=O)OC2=CC=C(C=C2)[N+](=O)[O-])NC(=O)CCCCCN3C(=O)C=CC3=O

InChI

1S/C35H43N7O11/c1-22(2)31(40-28(43)8-4-3-5-20-41-29(44)17-18-30(41)45)33(47)39-27(7-6-19-37-34(36)48)32(46)38-24-11-9-23(10-12-24)21-52-35(49)53-26-15-13-25(14-16-26)42(50)51/h9-18,22,27,31H,3-8,19-21H2,1-2H3,(H,38,46)(H,39,47)(H,40,43)(H3,36,37,48)/t27-,

InChIKey

HYSPJPGXSALJRR-DHIFEGFHSA-N

Density

1.338±0.06 g/cm3

Solubility

Soluble in DMSO, not soluble in water

Flash Point

579.4±34.3 °C

Index Of Refraction

1.599

PSA

261.15000

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

Solid powder

Quantity

Grams-Kilos

Shelf Life

2 years

Shipping

Room temperature

Storage

Store in a cool and dry place and at 0 - 4°C for short term (days to weeks) or -20°C for long term (months to years).

Boiling Point

1034.5±65.0 °C | Condition: Press: 760 Torr

Mc-Val-Cit-PABC-PNP is a protease-cleavable ADC linker widely used in the design of antibody-drug conjugates. It features a valine-citrulline (Val-Cit) dipeptide sequence coupled to a para-aminobenzyl carbamate (PABC) self-immolative spacer and a para-nitrophenyl (PNP) activated ester, providing precise conjugation points for ADC cytotoxins. This structure enables controlled payload release upon enzymatic cleavage by cathepsin B in the tumor microenvironment, supporting targeted drug delivery while maintaining stability in systemic circulation.

In ADC linker design, the Val-Cit dipeptide acts as a substrate for lysosomal proteases, ensuring selective release of the ADC payload within cancer cells. The PABC self-immolative spacer transduces enzymatic cleavage into rapid cytotoxin release, enhancing the potency of the ADC. The PNP ester functionality facilitates efficient coupling to antibodies, allowing reproducible attachment and defined drug-to-antibody ratios (DAR), which are critical for consistent ADC performance.

The chemical stability of Mc-Val-Cit-PABC-PNP in plasma prevents premature payload release, while the cleavable dipeptide ensures payload activation specifically in the tumor environment. Its compatibility with a wide range of cytotoxic ADC payloads, including auristatins and maytansinoids, makes it a versatile tool in oncology-focused bioconjugation and ADC development workflows.

This protease-cleavable linker is widely applied in ADC research to optimize therapeutic index, improve tumor specificity, and maintain antibody functionality. Its combination of enzymatic sensitivity, self-immolative spacer, and efficient coupling chemistry provides a robust platform for constructing high-performance antibody-drug conjugates with controlled payload release and reproducible pharmacokinetics.

1. EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy

Yanyan Liu, Yuanfen Liu, Yue Zhang, Jiasheng Tu, Zixuan Ye, Yan Shen Int J Nanomedicine . 2021 Mar 26;16:2443-2459. doi: 10.2147/IJN.S289228.

Background:Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab-valine-citrulline (vc)-doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells.Methods:Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody-drug conjugates (ADCs). Then, the ADCs were adsorbed to the surface of the BSA nanoparticles (NPs), which were prepared by a desolvation method to obtain cetuximab-vc-DOX-BSA-NPs. The cetuximab-vc-DOX conjugates adsorbed on the surface of the BSA nanoparticles were determined and optimized by size exclusion chromatography. An in vitro cytotoxicity study was conducted using a colon carcinoma cell line with different EGFR-expression levels to test the selectivity of cetuximab-vc-DOX-NPs.Results:The vc-DOX and cetuximab-vc-DOX conjugates were both synthesized successfully and their structural characteristics confirmed by1H-NMR and SDS-PAGE. The MTT assay showed stronger cytotoxicity of cetuximab-vc-DOX-NPs versus control IgG-vc-DOX-NPs in EGFR-overexpressing RKO cells. Cellular binding and intracellular accumulation determined by flow cytometry and confocal laser scanning microscopy revealed the strong binding ability of cetuximab-vc-DOX-NPs to RKO cells. The in vivo imaging study demonstrated that cetuximab-vc-DOX-NPs exhibited higher fluorescent intensity in tumor tissues than non-decorated nanoparticles (IgG-vc-DOX-NPs). In vivo tumor inhibition and survival tests showed that cetuximab-vc-DOX-NPs revealed higher tumor inhibition efficacy and lower systemic toxicity than control IgG-vc-DOX- NPs.Conclusion:The obtained results emphasize that cetuximab-vc-DOX-NPs, with good tumor-targeting ability and low systemic toxicity, are a promising targeting system for drug delivery.

2. Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies

Weirong Lai, Mengdan Wu, Jinliang Yang, Lantu Gou, Hao Chen, Yuxi Wang, Yiwen Zhang, Ruixue Wang, Yujia Peng, Cuiyu Guo, Ruirui Zhang, Ying Lu, Yuyin Fu, Wei Liao, Qinhuai Lai, Yuqin Yao, Xiaohua Jiang, Lin Yu, Xin Wang, Tairan Kang, Zhixiong Zhang, Yiran Tao Eur J Med Chem . 2020 Aug 1;199:112364. doi: 10.1016/j.ejmech.2020.112364.

Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50values at low nanomolar levels (0.58-1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI-N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy.

What is Mc-Val-Cit-PABC-PNP?

Mc-Val-Cit-PABC-PNP is a protease-cleavable linker commonly used in ADCs. It features a Val-Cit dipeptide recognized by lysosomal enzymes, and a PABC-PNP self-immolative spacer that facilitates controlled drug release upon internalization into target cells.

27/8/2018

Dear BOC Sciences, why is Mc-Val-Cit-PABC-PNP important for ADC efficacy?

Mc-Val-Cit-PABC-PNP enables selective payload release in lysosomes of target cells. Its enzymatically cleavable dipeptide ensures that cytotoxic agents are released only after cellular uptake, reducing systemic toxicity and improving therapeutic index.

9/12/2019

Dear BOC Sciences, how should Mc-Val-Cit-PABC-PNP be stored?

Store Mc-Val-Cit-PABC-PNP at -20°C under an inert atmosphere. Protecting it from moisture and light prevents degradation and preserves the enzymatically cleavable functionality critical for controlled payload release.

19/9/2021

Dear BOC Sciences, are supporting documents available for Mc-Val-Cit-PABC-PNP?

BOC Sciences provides full analytical documentation, including certificates of analysis (CoA), NMR, and LC-MS data, ensuring researchers can validate chemical integrity and conjugation suitability.

16/2/2016

Dear BOC Sciences, which analytical methods are suitable for Mc-Val-Cit-PABC-PNP?

Verification is commonly performed with HPLC, LC-MS, and NMR spectroscopy to confirm the structural integrity of the peptide linker and its reactive PNP group for conjugation applications.

29/8/2017

— Dr. James Carter, Senior Scientist (USA)

Mc-Val-Cit-PABC-PNP proved invaluable for our ADC conjugation studies. Its purity and lot consistency allowed reproducible results.

19/9/2021

— Prof. Anna Müller, Biochemistry Researcher (Germany)

The delivery of Mc-Val-Cit-PABC-PNP was prompt and the product met all our analytical requirements. Excellent supplier!

29/8/2017

— Dr. Michael Thompson, ADC Scientist (UK)

Using Mc-Val-Cit-PABC-PNP, we achieved high conjugation efficiency without optimization. Truly a reliable product.

16/2/2016

— Ms. Emily Johnson, Research Associate (Canada)

The stability and solubility of Mc-Val-Cit-PABC-PNP were excellent, making multi-step ADC synthesis smooth.