TH 5487

TH5487 is a potent 8-oxoguanine DNA glycosylase 1 (OGG1) inhibitor with an IC50 of 342 nM. TH5487 stops OGG1 from recognizing its DNA substrate, inhibits DNA repair and modifies OGG1 chromatin dynamics, which results in the inhibition of proinflammatory pathway genes[1].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

TH5487 (5 μM; 1 hour) decreases TNFα- and LPS-induced proinflammatory gene expression to near pretreatment levels[1]. TH5487 (0-10 μM; 1 hour) perturbs binding of NF-κB to 8-oxoG–containing synthetic DNA in nuclear extracts from MLE 12 or hSAEC cells[1]. RT-PCR[1] Cell Line: Murine airway epithelial cell line (MLE 12); Diploid human small-airway epithelial cell (hSAECs) Concentration: 5 μM Incubation Time: 1 hour Result: Inhibited proinflammatory gene expression dose-dependently. Western Blot Analysis[1] Cell Line: Murine airway epithelial cell line (MLE 12); Diploid human small-airway epithelial cell (hSAECs) Concentration: 2.5 μM; 5 μM; 10 μM Incubation Time: 1 hour Result: Decreased p50-p65 and p50-p50 expression in a dose dependent manner.

TH5487 (prophylactic intraperitoneally injection; 8-30 mg/kg; 1-9 hours) decreases TNFα or LPS induced the robust recruitment of neutrophils to the airways, and reduces the pulmonary neutrophil count in a time-dependent manner[1]. Animal Model: Eightweek-old female and male BALB/c mice[1] Dosage: 8 mg/kg, 15 mg/kg, 30 mg/kg Administration: Prophylactic intraperitoneally injection; 8-30 mg/kg; 1-9 hours Result: InterruptedTNFα-induced ongoing inflammatory processes.

[1]. Visnes T, et al. Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation. Science. 2018 Nov 16;362(6416):834-839.