159858-08-9

Upstream product

• 7693-46-1 4-Nitrophenyl chloroformate 
• 159858-07-8 N-Cbz-Val-Cit-4-aminobenzyl alcohol 
• 3496-11-5 2,5-dioxopyrrolidin-1-yl (2S)-2-(((benzyloxy)carbonyl)amino)-3-methylbutanoate 
• 1149-26-4 (S)-N-(benzyloxycarbonyl)valine 
• 623-04-1 4-aminobenzenemethanol 
• 159858-06-7 N-[(Benzyloxy)carbonyl]-L-valyl-N₅-carbamoyl-L-ornithine 
• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 133174-15-9 (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid 
• 501-53-1 benzyl chloroformate 
• 1037794-22-1 (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide 
• 870487-04-0 (S)-(9H-fluoren-9-yl)methyl (1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate 
• 72-18-4 L-valine 

Downstream Products

• 1613321-00-8 (2S,3S,4R)-1-O-(α-D-galactopyranosyl)-4-O-(hexacosanoyl)-2-(((N-Cbz-Val-Cit-4-aminobenzyloxy)carbonyl)amino)octadecane-1,3,4-triol 

Relevant academic research and scientific papers

Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity

Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.

CONJUGATE COMPOUNDS

The invention relates to sphingoglycolipid analogues and peptide derivatives thereof, which are useful in treating or preventing diseases or such as those relating to infection, atopic disorders, autoimmune diseases or cancer.

Cathepsin B-sensitive dipeptide prodrugs. 1. A model study of structural requirements for efficient release of doxorubicin

A series of lysosomal protease-sensitive peptides attached to doxorubicin (DOX) was prepared as model substrates for internalizing anticancer immunoconjugates and potential antimetastasis prodrugs. Rates of cathepsin B-mediated release of free drug was measured for each, and human plasma stabilities for representative examples.