WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 463689
CAS#: 2210228-45-6
Description: SU0268 is a potent and selective OGG1 inhibitor. DNA glycosylases involved in the first step of the DNA base excision repair pathway are promising targets in cancer therapy. There is evidence that reduction of their activities may enhance cell killing in malignant tumors.
MedKoo Cat#: 463689
Name: SU0268
CAS#: 2210228-45-6
Chemical Formula: C26H25N3O4S
Exact Mass: 475.1566
Molecular Weight: 475.563
Elemental Analysis: C, 65.67; H, 5.30; N, 8.84; O, 13.46; S, 6.74
Synonym: SU0268; SU 0268; SU-0268;
IUPAC/Chemical Name: 4'-(N-(1-(cyclopropanecarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)sulfamoyl)-[1,1'-biphenyl]-3-carboxamide
InChi Key: XGGNCZLDTJOSFV-UHFFFAOYSA-N
InChi Code: InChI=1S/C26H25N3O4S/c27-25(30)21-4-1-3-20(15-21)17-9-12-23(13-10-17)34(32,33)28-22-11-8-18-5-2-14-29(24(18)16-22)26(31)19-6-7-19/h1,3-4,8-13,15-16,19,28H,2,5-7,14H2,(H2,27,30)
SMILES Code: O=C(C1=CC(C2=CC=C(S(=O)(NC3=CC4=C(C=C3)CCCN4C(C5CC5)=O)=O)C=C2)=CC=C1)N
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | OGG1 Inhibitor O8 is a potent inhibitor of 8-Oxoguanine DNA Glycosylase-1 (OGG1) |
| In vitro activity: | Optimization of the tetrahydroquinoline scaffold over five regions of the structure ultimately yielded amidobiphenyl compound 41 (SU0268; IC50 = 0.059 μM). SU0268 was confirmed by surface plasmon resonance studies to bind the enzyme both in the absence and in the presence of DNA. The compound SU0268 was shown to be selective for inhibiting OGG1 over multiple repair enzymes, including other base excision repair enzymes, and displayed no toxicity in two human cell lines at 10 μM. Finally, experiments confirm the ability of SU0268 to inhibit OGG1 in HeLa cells, resulting in an increase in accumulation of 8-OG in DNA. The results suggest the compound SU0268 as a potentially useful tool in studies of the role of OGG1 in multiple disease-related pathways. Reference: Tahara YK, Auld D, Ji D, Beharry AA, Kietrys AM, Wilson DL, Jimenez M, King D, Nguyen Z, Kool ET. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018 Feb 14;140(6):2105-2114. doi: 10.1021/jacs.7b09316. Epub 2018 Feb 5. PMID: 29376367; PMCID: PMC5823510. |
| In vivo activity: | A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, it was reported that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during Pseudomonas aeruginosa (PA14) infection, which is mediated by the KRAS-ERK1-NF-κB signaling pathway. Furthermore, 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. Collectively, the results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection. Reference: Qin S, Lin P, Wu Q, Pu Q, Zhou C, Wang B, Gao P, Wang Z, Gao A, Overby M, Yang J, Jiang J, Wilson DL, Tahara YK, Kool ET, Xia Z, Wu M. 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. doi: 10.4049/jimmunol.1901533. Epub 2020 Sep 14. PMID: 32929043; PMCID: PMC7541742. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 10.51 |
The following data is based on the product molecular weight 475.563 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | Tahara YK, Auld D, Ji D, Beharry AA, Kietrys AM, Wilson DL, Jimenez M, King D, Nguyen Z, Kool ET. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018 Feb 14;140(6):2105-2114. doi: 10.1021/jacs.7b09316. Epub 2018 Feb 5. PMID: 29376367; PMCID: PMC5823510. |
| In vitro protocol: | Tahara YK, Auld D, Ji D, Beharry AA, Kietrys AM, Wilson DL, Jimenez M, King D, Nguyen Z, Kool ET. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018 Feb 14;140(6):2105-2114. doi: 10.1021/jacs.7b09316. Epub 2018 Feb 5. PMID: 29376367; PMCID: PMC5823510. |
| In vivo protocol: | Qin S, Lin P, Wu Q, Pu Q, Zhou C, Wang B, Gao P, Wang Z, Gao A, Overby M, Yang J, Jiang J, Wilson DL, Tahara YK, Kool ET, Xia Z, Wu M. 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. doi: 10.4049/jimmunol.1901533. Epub 2020 Sep 14. PMID: 32929043; PMCID: PMC7541742. |
1: Kant M, Tahara YK, Jaruga P, Coskun E, Lloyd RS, Kool ET, Dizdaroglu M. Inhibition by Tetrahydroquinoline Sulfonamide Derivatives of the Activity of Human 8-Oxoguanine DNA Glycosylase (OGG1) for Several Products of Oxidatively induced DNA Base Lesions. ACS Chem Biol. 2020 Dec 17. doi: 10.1021/acschembio.0c00877. Epub ahead of print. PMID: 33331782.
2: Qin S, Lin P, Wu Q, Pu Q, Zhou C, Wang B, Gao P, Wang Z, Gao A, Overby M, Yang J, Jiang J, Wilson DL, Tahara YK, Kool ET, Xia Z, Wu M. 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. doi: 10.4049/jimmunol.1901533. Epub 2020 Sep 14. PMID: 32929043; PMCID: PMC7541742.
3: Tahara YK, Auld D, Ji D, Beharry AA, Kietrys AM, Wilson DL, Jimenez M, King D, Nguyen Z, Kool ET. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018 Feb 14;140(6):2105-2114. doi: 10.1021/jacs.7b09316. Epub 2018 Feb 5. PMID: 29376367; PMCID: PMC5823510.
