RPA Inhibitor, TDRL-505 - Calbiochem

General Description

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.

Biochem/physiol Actions

Cell permeable: yes

Raw materials

Preparation Products