RPA Inhibitor, TDRL-505

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.

Cell permeable: yes

Primary Target
Replication Protein A

Reversible: yes

Target IC₅₀: 12.9, 15.7 and 30.8 &micro

Packaged under inert gas

Use only fresh DMSO for reconstitution.

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

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

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

Toxicity: Standard Handling (A)