SU0268

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].

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

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]. Cell Viability Assay[1] Cell Line: A549 shGFP and shMTH1 (2000 cells per well). Concentration: 0.1 μM, 0.5 μM, 1 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM. Incubation Time: 24 or 48 h. Result: The shGFP cells were more susceptible to OGG1 inhibition via increasing SU0268 doses than the shMTH1 cells, especially at the 48 time-point.

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]. Animal Model: Anesthetized C57BL/6N mice[3]. Dosage: 10 mg/kg. Administration: Intranasally treated. Result: Significantly inhibits inflammatory responses and mitigates P. aeruginosa infection.

[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.