TH10785

TH10785 is a DNA glycosylase 1 (OGG1) activator, TH10785 can interact with the phenylalanine-319 and glycine-42 amino acids of OGG1 and increase the enzyme activity, generates β,δ-lyase enzymatic function. TH10785 can control the catalytic activity mediated by a nitrogen base within its molecular structure. TH10785 can be used for the research of various diseases and aging connected with DNA oxidative lesions[1].

Research Areas >> Others

Signaling Pathways >> Others >> Others

OGG1 (KD=5.5 μM)[1]

TH10785 induces a de novo β,δ-elimination in vitro, allowing for AP sites as new substrates. TH10785 allows OGG1 to increase DNA repair by addressing AP sites. TH10785-induced OGG1 β,δ-lyase activity shifts cells toward PNKP1 dependence. TH10785 has affinity to OGG1 (KD=5.5 μM) increased when adding an AP site analog containing double-stranded DNA (KD = 1.3 μM)[1]. Cell Viability Assay[1] Cell Line: U2OS cells Concentration: 0-20 μM Incubation Time: 72 hours Result: Reduced combination with PNKP1 inhibition for TH10785. Western Blot Analysis[1] Cell Line: U2OS cells Concentration: 10 μM Incubation Time: 24 h Result: Caused an up-regulation of members of the DDR through b,d-elimination in combination with PNKP1 inhibition. RT-PCR[1] Cell Line: U2OS cells Concentration: 10 μM Incubation Time: 1 h Result: Decreased oxidative damage in guanine-rich regions of the genome. Immunofluorescence[1] Cell Line: U2OS OGG1-GFP cells Concentration: 1 μM Incubation Time: 0-2 min Result: ecruited more OGG1 to laser-damaged sites.

[1]. Maurice Michel, et al. Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function. Science. 2022 Jun 24;376(6600):1471-1476.