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

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

Used in Pharmaceutical Industry:
FMoc-Val-Cit-PAB is used as a cleavable ADC linker for the targeted delivery of therapeutic agents to cancer cells. The application reason is that the Val-Cit sequence is specifically cleaved by Cathepsin B, an enzyme present in the lysosome, ensuring the selective release of the ADC payload within the target cell. This targeted approach minimizes damage to healthy cells and enhances the therapeutic efficacy of the drug.
Additionally, the Fmoc group can be deprotected under basic conditions, allowing for the controlled release of the drug payload and further customization of the ADC for specific applications.

Upstream product

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

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 
• 1611498-13-5 C₂₉H₄₂N₆O₁₁S₂ 
• 1611498-14-6 C₃₆H₄₅N₇O₁₅S₂ 
• 159857-80-4 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide 
• 159857-81-5 N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-N⁵-carbamoyl-N[4-({[(4-nitrophenoxy)carbonyl]oxy}methyl)phenyl]-L-ornithinamide 

Relevant articles and documents

Linker, Antibody-Drug Conjugate Including Same and Use Thereof

Provided are a linker represented by Formula I or I′, an antibody-drug conjugate containing the same, and use of thereof, a pharmaceutical composition comprising the antibody-drug conjugate, and use of the antibody-drug conjugate for treating and/or preventing a disease.

CYCLIC DINUCLEOTIDE STING AGONISTS TETHERED TO A PD-1 OR CTLA-4 ANTIBODIES

Disclosed are antibody-drug conjugates and compositions thereof for the activation or induction of expression of a pattern recognition receptor (e.g., STING, RIG-I, MDA5), and methods of use thereof.

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.

Synthesis, characterization, and targeted chemotherapy of SCT200-linker-monomethyl auristatin E conjugates

Antibody-drug conjugates (ADCs) are currently among the most successful and important strategies for treating patients with solid tumors. ADCs are composed of a monoclonal antibody and warhead, which are conjugated via a linker. Currently, monomethyl auristatin E (MMAE) is the most widely applied warhead in the development of ADCs. However, MMAE-based ADCs are generally constructed using the MC-VC-PABC linker, and this design has limited structural diversity and some disadvantages. Accordingly, in this study, we generated three types of novel linker-MMAE (with alterations in the spacer, catabolizing area, and self-immolative compared with MC-VC-PABC-MMAE) in ADCs, termed SCT200-linker-MMAE conjugates, and then evaluated the linker-drug plasma stability and the rate of drug release by cathepsin B. The binding ability, internalization rates, and efficacy of all SCT200-linker-MMAE ADCs were systematically studied, and the expression of apoptosis-associated proteins and the therapeutic efficacies of SCT200-M-2, -C-2, and -C-4 were evaluated. The results showed that the activities of some of these ADCs were increased for epidermal growth factor receptor-positive tumors. Moreover, the novel linkers designed in this study can be linked with other antibodies to treat other types of cancer. Overall, these findings provide important insights into the application of SCT200-based linkers in 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

PROTEIN-ANTIVIRAL COMPOUND CONJUGATES

Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with influenza, including VX-787 and derivatives thereof, baloxavir and derivatives thereof, and baloxavir marboxil and derivatives thereof, and protein (e.g., antibody) drug conjugates thereof.

COMPOUNDS, COMPOSITIONS, METHODS, AND USES FOR TREATING CANCER AND IMMUNOLOGICAL DISORDERS

The present disclosure provides novel polypeptide-therapeutic compound or hormone-therapeutic compound conjugates using cleavable or non-cleavable linkers, whereby the polypeptide or hormone serves to target specific cells using receptor expression on the targeted cell to bind the ligand (polypeptide or hormone) carrying the therapeutic compound unlike antibody drug conjugates. Upon binding, the ligand and the therapeutic compound (multiples of the therapeutic compound in some embodiments) enter the cell by receptor-mediated endocytosis, and release drugs conjugated to the ligand by linkers, to interact with intracellular components to enhance, restore, or block a signal transduction process. The ligands for the polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: cytokines, growth factors and hormones among other proteins with corresponding cell surface specific receptors. The disorders targeted by such polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: immunological disorders (e.g., allergy and autoimmune disorders) and cancer.

BIOACTIVE CONJUGATE, PREPARATION METHOD THEREFOR AND USE THEREOF

The disclosure relates to a bioactive molecule conjugate, preparation methods and use thereof, particularly relates to a novel bioactive molecule conjugate obtained by improving coupling of the drug and the targeting moiety in an ADC or SMDC, as well as its preparation method and use in the manufacture of a medicament for the treatment of a disease associated with an abnormal cell activity.

LINKERS AND CONJUGATES

A conjugate comprising a protein or a peptide, a linker and an active agent, wherein the linker comprises the moiety of formula (III): (III) wherein two of A1, A2 and A3 are N and the other of A1, A2