159858-22-7

Basic information

• Product Name: FMoc-Val-Cit-PAB
• Synonyms: FMoc-Val-Cit-PAB
• CAS NO: 159858-22-7
• Molecular Formula: C₃₃H₃₉N₅O₆
• Molecular Weight: 601.69
• Mol File: 159858-22-7.mol
• Article Data: 28

Chemical Properties

• Melting Point: 204 °C(dec.)
• Boiling Point: 914.2±65.0 °C(Predicted)
• Appearance: /
• Density: 1.276±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: 10.63±0.46(Predicted)
• CAS DataBase Reference: FMoc-Val-Cit-PAB(CAS DataBase Reference)
• NIST Chemistry Reference: FMoc-Val-Cit-PAB(159858-22-7)
• EPA Substance Registry System: FMoc-Val-Cit-PAB(159858-22-7)

Safety Data

• Hazardous Substances Data: 159858-22-7(Hazardous Substances Data)

Usage

Uses

Fmoc-Val-Cit-PAB is a commonly used bridge for a degradable antibody-conjugated drug (ADC).

Description

Fmoc-Val-Cit-PAB-OH is a cleavable ADC linker. The Val-Cit will specifically be cleaved by Cathepsin B. As this enzyme is only present in the lysosome, the ADC payload will be released only in the cell. Fmoc can be deprotected under basic condition.

Upstream product

• 68858-20-8 Fmoc-Val-OH 
• 130878-68-1 2,5-dioxopyrrolidin-1-yl-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valinate 
• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 6692-89-3 N^α-benzyloxy-carbonyl-L-citrulline 
• 372-75-8 Citrulline 
• 623-04-1 4-aminobenzenemethanol 
• 870487-04-0 (S)-(9H-fluoren-9-yl)methyl (1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate 
• 133174-15-9 (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid 
• 1037793-80-8 (S)-tert-butyl 1-(4-(hydroxymethyl)phenylamino)-1-oxo-5-ureidopentan-2-ylcarbamate 
• 1037794-22-1 (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide 
• 159858-21-6 (S)-2-((S)-2-((((9H-fluoren-9-yl)-methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanoic acid 

Downstream Products

• 863971-53-3 (9H-fluoren-9-yl)methyl ((S)-3-methyl-1-(((S)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-1-oxobutan-2-yl)carbamate 
• 646502-53-6 4-((R)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((2S)-1-(((2S)-1-(((4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate 
• 1639351-92-0 N-((S)-1-(((S)-1-((4-(chloromethyl)phenyl)amino)-1-oxo-5-ureidopentan- 2-yl)amino)-3-methyl-1-oxobutan-2-yl)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamide 

Relevant articles and documents

A Wireframe DNA Cube: Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E

In recent years, several antibody drug conjugates (ADC) have been accepted by the FDA as therapeutics against cancer. It is well-known that control of drug-to-antibody ratio (DAR) is vital for the success of an ADC, which inspires the advancement of bette

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.

ANTIBODY-DRUG CONJUGATE

Provided herein is an antibody-drug conjugate (ADC) especially a PEGylated mono or bispecific antibody-drug conjugate (BsADC) prepared with site-specific conjugation to provide homogeneous conjugate with high potency and low toxicity. It also relates to a