1639939-40-4

Basic information

• Product Name: [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate
• CAS NO: 1639939-40-4
• Molecular Weight: 651.673
• Mol File: 1639939-40-4.mol

Chemical Properties

• CAS DataBase Reference: [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate(CAS DataBase Reference)
• NIST Chemistry Reference: [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate(1639939-40-4)
• EPA Substance Registry System: [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate(1639939-40-4)

Safety Data

• Hazardous Substances Data: 1639939-40-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate is used as a building block for the synthesis of novel pharmaceutical compounds. Its unique structure and functional groups can be exploited to create new drugs with specific therapeutic properties.
Used in Chemical Research:
In the field of chemical research, [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate serves as a valuable compound for studying the reactivity and interactions of its various functional groups. This can lead to a better understanding of similar complex molecules and their potential applications.
Used in Biochemical Applications:
[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate's amino acid-derived side chains and unique structure make it a candidate for use in biochemical applications, such as enzyme inhibition or modulation of protein-protein interactions. Its specific functional groups can be tailored to target specific biological processes or pathways.
Used in Material Science:
The complex structure of [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate may also find applications in material science, where its unique properties can be utilized to develop new materials with specific characteristics, such as improved stability or reactivity.

Upstream product

• 130878-68-1 2,5-dioxopyrrolidin-1-yl-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valinate 
• 150114-97-9 N-(9-fluorenylmethoxycarbonyl)-L-valyl-L-alanine 
• 1394238-91-5 (9H-fluoren-9-yl)methyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)- 1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 
• 1343476-44-7 (9H-fluoren-9-yl)methyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 
• 1870916-87-2 6-(2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)-N-[(S)-1-{[(S)-1-{[4-(hydroxymethyl)phenyl] amino}-1-oxopropan-2-yl]amino}-3-methyl-1-oxobutan-2-yl]hexanamide 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 55750-63-5 6-maleimidohexanoic acid N-hydroxylsuccinimide ester 
• 68858-20-8 Fmoc-Val-OH 
• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 60-32-2 6-aminohexanoic acid 
• 55750-53-3 2,5-Dihydro-2,5-dioxo-1H-pyrrole-1-hexanoic acid 

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.

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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.

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