5.30535

RPA Inhibitor, TDRL-505

• Sinónimos: RPA Inhibitor, TDRL-505, Replication Protein A Inhibitor, Pot1 Inhibitor, Protection of Telemeres Protein 1 Inhibitor, TDRL505
• Fórmula empírica (notación de Hill): C₂₄H₂₁BrClN₃O₄
• Número de CAS: 1785760-75-9
• Peso molecular: 530.80
• Código UNSPSC: 12352200
• ID de la sustancia en PubChem: 5212392
• NACRES: NA.77

Propiedades

• Ensayo: ≥97% (HPLC)
• Nivel de calidad: 100
• Formulario: solid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: off-white
• solubilidad: DMSO: 50 mg/mL
• temp. de almacenamiento: −20°C
• cadena SMILES: CCOC1=CC2=NC(=C(C=C2C=C1)C3CC(=NN3C(=O)CCC(=O)O)C4=CC=C(C=C4)Br)Cl

Descripción

Descripción general

A cell-permeable quinolinyl-dihydropyrazolyl-oxobutanoic acid compound that is shown to target human Replication Protein A (RPA) via primarily the oligosaccharide/oligonucleotide-binding (OB) folds of DNA-bonding domains A & B (DBD-A/B) in the p70 subunit, effectively inhibiting its DNA-binding activity as well as that of Schizosaccharomyces pombe telemere end-binding protein Pot1 (IC₅₀= 12.9 µM and 15.7 µM, respectively), but not Xeroderma pigmentosum group A protein (XPA) involved in the nucleotide excision repair (NER) pathway or E. coli SSB. Reported to induce cell cycle G1-arrest and decrease Annvex V^-/PI^- healthy cell population (by 50%; 30.8 µM for 48 h) in H460 non-small cell lung carcinoma (NSCLC) cultures with minimal cytotoxicity against freshly isolated human PBMC. Potentiates cisplatin (Cat. No. 232120) and etopside (Cat. No. 341205) cytotoxicity in H460 cultures in a synergistic manner.

A cell-permeable quinolinyl-dihydropyrazolyl-oxobutanoic acid compound that is shown to target human Replication Protein A via primarily the oligosaccharide/oligonucleotide-binding (OB) folds of DNA-bonding domains A & B (DBD-A/B) in the p70 subunit, effectively inhibiting its DNA-binding activity as well as that of Schizosaccharomyces pombe telemere end-binding protein Pot1 (IC₅₀= 12.9 µM/25 nM hRPA/25 nM 34-base AG-rich ssDNA and 15.7 µM/20 nM SpPot1 DBD/25 nM 15-base ssDNA), but not Xeroderma pigmentosum group A protein (XPA) involved in the nucleotide excision repair (NER) pathway or E. coli SSB (20% inhibition at 100 µM against 3.3 nM EcSSB & 25 nM 3Pc3 ssDNA binding). Reported to cause decreased nuclear RPA staining (50 µM for 3 h), cell cycle G1-arrest (75 to 100 µM), and a drop in Annvex V^-/PI^- healthy cell population (by 50%; 30.8 µM for 48 h) in H460 non-small cell lung carcinoma (NSCLC) cultures with minimal cytotoxicity against freshly isolated human PBMC. Potentiates cisplatin (Cat. No. 232120) and etopside (Cat. No. 341205) cytotoxicity in H460 cultures in a synergistic manner, consistent with blockage of RPA-mediated NER pathway.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
Replication Protein A

Reversible: yes

Target IC₅₀: 12.9, 15.7 and 30.8 &micro

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Use only fresh DMSO for reconstitution.

Otras notas

Anciano Granadillo, V.J., et al. 2010. J. Nucleic Acids2010, 304035.

Shuck, S.C., and Turchi, J.J. 2010. Cancer Res.70, 3189.

Información legal

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable