Synonyms: TH-5487
Compound class:
Synthetic organic
Comment: TH5487 is a selective, active-site inhibitor of 8-oxoguanine DNA glycosylase (OGG1) [2]. OGG1 repairs 8-hydroxy-2′-deoxyguanosine (8-oxoG) DNA defects that can be induced by reactive oxygen species (ROS) at sites of inflammation. TH5487 inhibits OGG1-mediated proinflammatory activity in allergic states. In a mouse model of allergic airway inflammation TH5487 reduced NF-κB-mediated expression of proinflammatory cytokines/chemokines and inhibited immune cell recruitment into the lungs with an associated reduction in goblet cell hyperplasia and mucus production [1].
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Immunopharmacology Comments |
TH5487 prevents TNF-α-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes and reduces NF-κB-dependent proinflammatory gene expression. This action mediates an antiinflammatory effect in an in vivo model of lung inflammation, as proof-of -concept that targeting oxidative DNA repair may be of therapeutic value for the prevention and/or treatment of inflammation [2]. |