1870916-87-2

Basic information

• Product Name: Mc-Val-Ala-PAB
• Synonyms: Mc-Val-Ala-PAB
• CAS NO: 1870916-87-2
• Molecular Formula: C25H34N4O6
• Molecular Weight: 486.56066
• Product Categories: Linker;ADC LINKER
• Mol File: 1870916-87-2.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: Mc-Val-Ala-PAB(CAS DataBase Reference)
• NIST Chemistry Reference: Mc-Val-Ala-PAB(1870916-87-2)
• EPA Substance Registry System: Mc-Val-Ala-PAB(1870916-87-2)

Safety Data

• Hazardous Substances Data: 1870916-87-2(Hazardous Substances Data)

Usage

General Description

Mc-Val-Ala-PAB is a chemical compound that consists of a peptide sequence composed of the amino acids valine (Val) and alanine (Ala) connected to para-aminobenzoic acid (PAB) through a linker molecule. It is commonly used as a component in the synthesis of antibody-drug conjugates, which are a type of targeted cancer therapy. The PAB moiety serves as the attachment point for the cytotoxic drug to specifically target cancer cells, while the peptide sequence aids in the stability and bioavailability of the compound. Mc-Val-Ala-PAB has shown promising results in preclinical studies and in clinical trials for its ability to selectively deliver the cytotoxic drug to cancer cells, leading to its potential for use in cancer treatment.

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Relevant articles and documents

Development of bifunctional anti-PD-L1 antibody MMAE conjugate with cytotoxicity and immunostimulation

In recent years, tumor immunotherapy, especially the combination of PD1/PD-L1 inhibitors and chemotherapy, has developed rapidly. However, the systemic side effects induced by chemotherapy remain a crucial problem that needs to be addressed. Antibody drug conjugates (ADCs) are exceptional target-specific prodrugs that greatly improve the therapeutic window of chemotherapy drugs. Therefore, designing PD-L1-targeting ADCs is an interesting research project. In this study, we confirmed for the first time that the commercial anti-PD-L1 antibody Atezolizumab has better endocytosis efficiencies than Avelumab, and was more suitable for ADC design. Then, the most popular cytotoxic payload MMAE was conjugated to Atezolizumab via a classical dipeptide (valine-alanine) linker to generate a bifunctional PD-L1 ADC (ADC 3). An in vitro cytotoxicity test indicated the potent tumor cell inhibitory activity of ADC 3, with EC50 values of 9.75 nM to 11.94 nM. In addition, a co-culture of PBMCs in vitro proved that ADC 3 retained the immune activation effect of the Atezolizumab antibody. Moreover, ADC 3 exhibited a higher tumor inhibition rate and tumor regression rate in humanized immune system mice. To the best of our knowledge, this is the most active PD-L1-ADC reported thus far, which may promote the development of immunotherapy and novel ADCs.

Development and properties of valine-alanine based antibody-drug conjugates with monomethyl auristatin E as the potent payload

Antibody-drug conjugates (ADCs), designed to selectively deliver cytotoxic agents to antigen-bearing cells, are poised to become an important class of cancer therapeutics. Human epithelial growth factor receptor (HER2) is considered an effective target for cancer treatment, and a HER2-targeting ADC has shown promising results. Most ADCs undergoing clinical evaluation contain linkers that have a lysosomal protease-cleavable dipeptide, of which the most common is valine-citrulline (VC). However, valine-alanine (VA), another dipeptide comprising two human essential amino acids, has been used in next generation ADCs loading new toxins, but the druggable properties of ADCs loaded the most popular monomethyl auristatin E (MMAE) remain to be further explored. In this study, we generated VA-based ADCs that connected MMAE to an anti-HER2 antibody. We studied the differences in the preparation process, in vitro stability, cathepsin B activity and in vitro cytotoxicity of VA-based ADC compared to the ADC of VC. VA had comparable performance to VC, which preliminarily displays its practicability. Additional efficacy and safety studies in a xenograft model indicate this novel ADC exerted potent anti-tumor activity and negligible toxicity. The results of this study show the application potential of VA-based ADC with MMAE as the payload.