1037794-22-1

Basic information

• Product Name: (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide
• Synonyms: (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide
• CAS NO: 1037794-22-1
• Molecular Weight: 280.327
• Mol File: 1037794-22-1.mol
• Article Data: 24

Chemical Properties

• CAS DataBase Reference: (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide(1037794-22-1)
• EPA Substance Registry System: (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide(1037794-22-1)

Safety Data

• Hazardous Substances Data: 1037794-22-1(Hazardous Substances Data)

Usage

General Description

(S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide is a chemical compound with a complex structure that consists of an amino group, a phenyl ring with a hydroxymethyl group, a ureido group, and a pentanamide group. (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide is a potential pharmacological agent with therapeutic applications, and its precise function and mechanisms of action are still under investigation. It may have the potential to interact with biological targets in the body, and further research is needed to fully understand its properties and potential uses in medicine or biochemistry.

Upstream product

• 870487-04-0 (S)-(9H-fluoren-9-yl)methyl (1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate 
• 110-89-4 piperidine 
• 6692-89-3 N^α-benzyloxy-carbonyl-L-citrulline 
• 1037793-80-8 (S)-tert-butyl 1-(4-(hydroxymethyl)phenylamino)-1-oxo-5-ureidopentan-2-ylcarbamate 
• 372-75-8 Citrulline 
• 133174-15-9 (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid 
• 623-04-1 4-aminobenzenemethanol 

Downstream Products

• 1037794-26-5 Fmoc-Cit-PABOH 
• 1608127-09-8 C₂₂H₃₃N₅O₆ 
• 1608127-10-1 C₅₀H₆₀N₆O₁₈ 
• 1022094-34-3 C₄₆H₅₆N₆O₁₆ 

Relevant articles and documents

Improved Methodology for the Synthesis of a Cathepsin B Cleavable Dipeptide Linker, Widely Used in Antibody-Drug Conjugate Research

Antibody-drug conjugates (ADCs) represent an emerging class of biopharmaceutical agents that deliver highly potent anticancer agents (payloads) selectively to tumors or components associated with the tumor microenvironment. The linker, responsible for the connection between the antibody and payload, is a crucial component of ADCs. In certain examples the linker is composed of a cleavable short peptide which imparts an additional aspect of selectivity. Especially prevalent is the cathepsin B cleavable Mc-Val-Cit-PABOH linker utilized in many pre-clinical ADC candidates, as well as the FDA approved ADC ADCETRIS (brentuximab vedotin). An alternative route for the synthesis of the cathepsin B cleavable Mc-Val-Cit-PABOH linker is reported herein that involved six steps from l-Citrulline and proceeded with a 50% overall yield. In this modified route, the spacer (a para-aminobenzyl alcohol moiety) was incorporated via HATU coupling followed by dipeptide formation. Importantly, this route avoided undesirable epimerization and proceeded with improved overall yield. Utilizing this methodology, a drug-linker construct incorporating a potent small-molecule inhibitor of tubulin polymerization (referred to as KGP05), was synthesized as a representative example.

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.

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.