500565-15-1

Basic information

• Product Name: 6-chloro-9-({4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-2-methoxyacridinium chloride
• CAS NO: 500565-15-1
• Molecular Formula: C₂₆H₂₈Cl₂N₄O₂
• Molecular Weight: 499.4321
• Mol File: 500565-15-1.mol

Chemical Properties

• Boiling Point: 603.7°C at 760 mmHg
• Flash Point: 318.9°C
• Vapor Pressure: 3.61E-15mmHg at 25°C
• CAS DataBase Reference: 6-chloro-9-({4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-2-methoxyacridinium chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 6-chloro-9-({4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-2-methoxyacridinium chloride(500565-15-1)
• EPA Substance Registry System: 6-chloro-9-({4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-2-methoxyacridinium chloride(500565-15-1)

Safety Data

• Hazardous Substances Data: 500565-15-1(Hazardous Substances Data)

Usage

Chemical compound

6-chloro-9-(4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]phenylamino)-2-methoxyacridinium chloride

Family

Acridine

Form

Cationic dye with a chloride salt form

Medical applications

Diagnostic tool for detecting nuclear acid sequences

Research applications

Used in molecular biology and biochemistry as a fluorescent stain for nucleic acids and proteins

Microbiology applications

Used to stain negatively charged cell structures such as cell walls and capsules

Upstream product

• 103-90-2 4-acetaminophenol 
• 86-38-4 6,9-dichloro-2-methoxyacridine 
• 76226-58-9 4-amino-2-((4-methylpiperazin-1-yl)methyl)phenol 
• 77726-01-3 N-[4-Hydroxy-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-acetamide 
• 109-01-3 1-methyl-piperazine 
• 50-00-0 formaldehyd 

Relevant articles and documents

Enhancing the activity of platinum-based drugs by improved inhibitors of ERCC1–XPF-mediated DNA repair

Purpose: The ERCC1–XPF 5′–3′ DNA endonuclease complex is involved in the nucleotide excision repair pathway and in the DNA inter-strand crosslink repair pathway, two key mechanisms modulating the activity of chemotherapeutic alkylating agents in cancer ce

Targeting DNA Repair in Tumor Cells via Inhibition of ERCC1-XPF

The ERCC1-XPF heterodimer is a 5′-3′ structure-specific endonuclease, which plays an essential role in several DNA repair pathways in mammalian cells. ERCC1-XPF is primarily involved in the repair of chemically induced helix-distorting and bulky DNA lesions, such as cyclobutane pyrimidine dimers (CPDs), and DNA interstrand cross-links. Inhibition of ERCC1-XPF has been shown to potentiate cytotoxicity of platinum-based drugs and cyclophosphamide in cancer cells. In this study, the previously described ERCC1-XPF inhibitor 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin-1-yl)methyl)phenol (compound 1) was used as a reference compound. Following the outcome of docking-based virtual screening (VS), we synthesized seven novel derivatives of 1 that were identified in silico as being likely to have high binding affinity for the ERCC1-XPF heterodimerization interface by interacting with the XPF double helix-hairpin-helix (HhH2) domain. Two of the new compounds, 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-cyclohexylpiperazin-1-yl)methyl)phenol (compound 3) and 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-(2-(dimethylamino)ethyl) piperazin-1-yl) methyl) phenol (compound 4), were shown to be potent inhibitors of ERCC1-XPF activity in vitro. Compound 4 showed significant inhibition of the removal of CPDs in UV-irradiated cells and the capacity to sensitize colorectal cancer cells to UV radiation and cyclophosphamide.

Computer-aided drug design of small molecule inhibitors of the ERCC1-XPF protein–protein interaction

The heterodimer of DNA excision repair protein ERCC-1 and DNA repair endonuclease XPF (ERCC1-XPF) is a 5′–3′ structure-specific endonuclease essential for the nucleotide excision repair (NER) pathway, and it is also involved in other DNA repair pathways. In cancer cells, ERCC1-XPF plays a central role in repairing DNA damage induced by chemotherapeutics including platinum-based and cross-linking agents; thus, its inhibition is a promising strategy to enhance the effect of these therapies. In this study, we rationally modified the structure of F06, a small molecule inhibitor of the ERCC1-XPF interaction (Molecular Pharmacology, 84, 2013 and 12), to improve its binding to the target. We followed a multi-step computational approach to investigate potential modification sites of F06, rationally design and rank a library of analogues, and identify candidates for chemical synthesis and in vitro testing. Our top compound, B5, showed an improved half-maximum inhibitory concentration (IC50) value of 0.49 μM for the inhibition of ERCC1-XPF endonuclease activit, and lays the foundation for further testing and optimization. Also, the computational approach reported here can be used to develop DNA repair inhibitors targeting the ERCC1-XPF complex.

TARGETING DNA REPAIR IN TUMOR CELLS VIA INHIBITION OF ERCC1-XPF

The current application relates to pyronaridine or 6-chloro-2-methoxyacridine analogs having binding affinity for the ERCC1-XPF hetero-dimerization interface. The compounds can be used for targeting DNA repair in tumor cells via ERCC1-XPF inhibition, ther