159857-81-5

Basic information

• Product Name: L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-
• Synonyms: L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-;Mc-Val-Cit-PABC-PNP;MC-VC-PAB-PNP;MC-VAL-CIT-PAB-PNB;MC-Val-Cit-PAB-PNP;Maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyl alcohol p-nitrophenyl carbonate;L-Ornithinamide;Maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyl alcohol p-nitrophenyl carbonate Mc-Val-Cit-PABC-PNP
• CAS NO: 159857-81-5
• Molecular Formula: C₃₅H₄₃N₇O₁₁
• Molecular Weight: 737.75622
• Product Categories: ADCs Linkers
• Mol File: 159857-81-5.mol
• Article Data: 22

Chemical Properties

• Boiling Point: 1034.5±65.0 °C(Predicted)
• Appearance: /
• Density: 1.338±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 13.24±0.70(Predicted)
• CAS DataBase Reference: L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-(159857-81-5)
• EPA Substance Registry System: L-OrnithinaMide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N5-(aMinocarbonyl)-N-[4-[[[(4-nitrophenoxy)carbonyl]oxy]Methyl]phenyl]-(159857-81-5)

Safety Data

• Hazardous Substances Data: 159857-81-5(Hazardous Substances Data)

Usage

Description

Mc-Val-Cit-PABC-PNP is a peptide linker molecule used in the synthesis of antibody-drug conjugates (ADCs). It contains a maleimidocaproyl (Mc) group that can be conjugated to an antibody and a p-nitrophenol (PNP) group that allows the peptide to be linked to anticancer compounds, such as doxorubicin or monomethyl auristatin E (MMAE; ). ADCs target specific cell populations to induce a selective response, such as cell death in cancer cells.

Uses

Mc-Val-Cit-PABC-PNP is a cathepsin cleavable ADC linker used in the synthesis of antibody-drug conjugates.

Upstream product

• 623-04-1 4-aminobenzenemethanol 
• 916746-27-5 N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-N⁵-carbamoyl-L-ornithine 
• 692739-25-6 pentafluorophenyl 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate 
• 60-32-2 6-aminohexanoic acid 
• 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 
• 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 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 1037794-22-1 (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide 
• 372-75-8 Citrulline 
• 159858-21-6 (S)-2-((S)-2-((((9H-fluoren-9-yl)-methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanoic acid 
• 55750-63-5 6-maleimidohexanoic acid N-hydroxylsuccinimide ester 
• 130878-68-1 2,5-dioxopyrrolidin-1-yl-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valinate 
• 159857-79-1 (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide 

Downstream Products

• 919995-57-6 maleimidocaproyl-Val-Cit-PAB-MeVal-Val-Dil-Dap-2-chloro-Phe-OH 
• 920017-31-8 maleimidocaproyl-val-Cit-p-aminobenzoyl-NMeVal-Val-Dil-Dap-phosphonophenylalanine 
• 920017-30-7 maleimidocaproyl-Val-Cit-p-aminobenzoyl-NMeVal-Val-Dil-Dap-phosphonophenylalanine 
• 920017-40-9 MC-Val-Cit-PAB-MeVal-Val-Dil-ODMB 
• 889880-95-9 MC-vc-PAB-(N,N'-2-acetamido-1,3-propanediamine-ethyl)-bis-4-amino-1,8-naphthalimide 
• 889881-02-1 MC-vc-PAB-( N,N'-(2-ethoxy-N-ethylethanamine)-bis-3-nitro-1,8-naphthalimide) 
• 889880-96-0 MC-vc-PAB-(N,N'-2-acetamido-1,3-ethanediamine-propyl)-bis-4-morpholino-1,8-naphthalimide 
• 889880-97-1 MC-vc-PAB-(N,N'-2-acetamido-1,2-propanediamine-ethyl)-bis-4-morpholino-1,8-naphthalimide 
• 889880-98-2 MC-vc-PAB-(N,N'-2-acetamido-1,3-ethanediamine-propyl)-bis-4-amino-1,8-naphthalimide 
• 889880-99-3 MC-vc-PAB-(N,N'-2-acetamido-1,2-propanediamine-ethyl)-bis-3-nitro-1,8-naphthalimide 
• 889881-00-9 MC-vc-PAB-(N,N'-2-acetamido-1,3-ethanediamine-propyl)-bis-3-nitro-1,8-naphthalimide 
• 889881-01-0 MC-vc-PAB-(N,N'-(4-aza-octanyl)-bis-3-nitro-1,8-naphthalimide) 
• 889881-05-4 MC-vc-PAB-(N,N'-(bis-aminoethyl-1,3-propanediamine)-bis-(4-N-methylpiperidine)-1,8 naphthalimide) 
• 646502-53-6 C₆₈H₁₀₅N₁₁O₁₅ 

Relevant articles and documents

Novel PIKK inhibitor antibody-drug conjugates: Synthesis and anti-tumor activity

Novel neolymphostin-based antibody-drug conjugate (ADC) precursors were synthesized either through amide couplings between both cleavable and non-cleavable linkers and neolymphostin derivatives, or through Cu(I)-catalyzed acetylene-azide click cycloaddito

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.

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.

ONE-POT PROCESS FOR PREPARING INTERMEDIATE OF ANTIBODY-DRUG CONJUGATE

The present invention relates to a “one-pot process” for preparing intermediate of antibody-drug conjugate. The preparation process provided by the present invention is simple in operation, and needs no such steps like concentration, washing and filtratio