SU0268 is a potent and specific inhibitor of 8-Oxoguanine DNA glycosylase 1 (OGG1). SU0268 regulates inflammatory responses during Pseudomonas aeruginosa infection[1][2][3].
MTH1-depleted cells are less sensitive to the OGG1-specific inhibitor, SU0268 (5-10 μM), than their control shGFP counterparts[1].SU0268/IACS-4759 (5-20 μM, 48h) co-treated cells are more viable than the correspondingly-treated IACS-4759- or SU0268-treated cells[1].SU0268 does not bind DNA and thus interacts with OGG1 specifically rather than its substrate[2].SU0268 induces the release of type I IFN by the mitochondrial DNA-cGAS-STING-IRF3-IFN-β axis, which decreases bacterial loads and halts disease progression[3].
SU0268 pretreatment (10 mg/kg, intranasally treated) increases survival rates compared with controls without SU0268 pretreatment in MH-S cells and C57BL/6N mice[3].
[1]. Ling Zhang, et al. OGG1 co-inhibition antagonizes the tumor-inhibitory effects of targeting MTH1. Redox Biol. 2021 Apr;40:101848.
[2]. Yu-Ki Tahara, et al. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018 Feb 14;140(6):2105-2114.
[3]. Shugang Qin, et al. Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during Pseudomonas aeruginosa Infection. J Immunol. 2020 Oct 15;205(8):2231-2242.