Obtusaquinone
Obtusaquinone is a blood-brain barrier-permeable Keap1 inhibitor with anticancer activity. Obtusaquinone covalently binds to cysteine residues of Keap1, promotes its ubiquitination and proteasomal degradation, and activates the Nrf2 pathway. Obtusaquinone induces endoplasmic reticulum stress and DNA damage through abnormal accumulation of ROS, and triggers apoptosis of cancer cells. Obtusaquinone prolongs survival in orthotopic xenograft models of pediatric high-grade glioma, and exhibits antitumor activity in glioblastoma and breast cancer models. Obtusaquinone can be used in studies related to glioma and breast cancer.
For research use only. We do not sell to patients.
- CAS No.: 21105-15-7
- Formula: C16H14O3
- Molecular Weight:254.28
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Obtusaquinone (OBT) (72 h) potently inhibits cell viability in patient-derived pHGG cell cultures (SU-DIPG-IV, SU-DIPG-VI, SU-DIPG-XIII, SU-GBM2, SJ-GBM2, CHLA-200) with IC50 values ranging from 659-1706 nM, and is significantly less toxic to human fibroblast culture MIN 33114 (IC50 = 16200 nM)[1].
Obtusaquinone (0.25-2 μM; 16 h treatment; 12 days recovery) inhibits long-term growth of SJ-GBM2 and CHLA-200 pediatric GBM cells[1].
Obtusaquinone (0.25 μM; 2-24 h) significantly reduces the motility of SJ-GBM2 and SU-DIPG-VI pHGG cells in a scratch wound healing assay[1].
Obtusaquinone (0.25-1 μM; 4 days treatment; 5 days recovery; 5 days secondary sphere formation incubation) inhibits neurosphere formation, recovery, and secondary sphere formation, reducing stem cell self-renewal in SU-DIPG-VI, SU-DIPG-XIII, and SU-GBM2 pHGG stem-like cells[1].
Obtusaquinone (100 nM-10 μM; 16 h for caspase 3/7 assay; 0.25-1 μM; 24 h for GFP-DEVD-ssGluc assay) induces caspase 3/7 activation in SJ-GBM2, SU-GBM2, SU-DIPG-VI, and SU-DIPG-XIII pHGG cells with EC50 values ranging from 368-1852 nM, and triggers dose-dependent apoptosis in SJ-GBM2 cells as measured by a GFP-DEVD-ssGluc sensor[1].
Obtusaquinone (100 nM-10 μM; 4 h for ROS EC50 determination; 0.5 μM plus 5 mM NAC; 4 h for rescue assay) induces dose-dependent ROS accumulation in SU-DIPG-IV, SU-DIPG-VI, SU-DIPG-XIII, and SU-GBM2 pHGG cells with EC50 values ranging from 374-1894 nM, and this ROS accumulation is reversed by co-treatment with 5 mM NAC in SJ-GBM2 cells[1].
Obtusaquinone (1-2.5 μM; 24 h) activates oxidative stress signaling (phosphorylated ERK1/2 and c-Jun), p53-mediated apoptotic pathways (elevated p53 and PUMA), and induces DNA double-strand breaks (phosphorylated γ-H2AX) in SJ-GBM2 pediatric GBM cells[1].
Obtusaquinone (0.1-0.5 μM; 2-8 h; 10 mM 4-Phenylbutyric acid pretreatment/co-treatment) induces dose- and time-dependent ER stress in SJ-GBM2 pediatric GBM cells, which is reversed by co-treatment with 10 mM 4-Phenylbutyric acid (HY-A0281) [1].
Obtusaquinone (0.25-2 μM; 1 mM 4-Phenylbutyric acid pretreatment/co-treatment) induces dose-dependent upregulation of ER stress marker genes (CHOP, sXBP1, BIP) and increases expression of ER stress-related proteins (p-EIF2α, BIP) in SJ-GBM2 pediatric GBM cells, with these effects reversed by co-treatment with 1 mM 4-Phenylbutyric acid[1].
Obtusaquinone (OBT) acts as an effective cysteine-alkylating reagent on bovine catalase, with binding reversibility dependent on the specific cysteine residue context[2].
Obtusaquinone covalently binds to multiple cysteine residues across Keap1 domains, with partial reversibility at Cys151 (BTB/CUL3 binding domain) and Cys434 (Kelch/Nrf2 binding domain)[2].
Obtusaquinone (1-3 μM; 4 days) dose-dependently reduces MDA-MB-231 breast cancer cell viability over 4 days of incubation[2].
Obtusaquinone upregulates HMOX1 and activates the Nrf2-Keap1 pathway via changes in the global proteome in GBM8 and BT07 glioma stemlike cells[2].
Obtusaquinone (0.25-2 μM; 8 h) dose-dependently upregulates HO1 mRNA expression in MDA-MB-231 breast cancer cells[2].
Obtusaquinone (16 h) activates the Nrf2-mediated ARE pathway in U87 glioma cells, with activation dependent on thiol reactivity[2].
Obtusaquinone (1-3 μM; 2-24 h) induces time- and dose-dependent degradation of Keap1 protein in U87 glioma cells, with maximal reduction observed at 3 μM after 8 h of incubation[2].
Obtusaquinone (2 μM; 6 h) induces ubiquitination of Keap1 in 293T cells expressing HA-Keap1, which is enhanced by proteasome inhibition with MG132[2].
Obtusaquinone (0.5-2 μM; 4 days) has significantly reduced cytotoxicity in U87 glioma cells with stable Keap1 knockdown compared to control cells after 4 days of incubation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:pediatric glioblastoma (GBM) cell lines SJ-GBM2, CHLA-200
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Concentration:0.25, 0.5, 1, 2 μM
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Incubation Time:16 h treatment; 12 days recovery
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Result:Significantly inhibited colony formation in SJ-GBM2 and CHLA-200 cells at 0.25 μM.
Completely abrogated colony formation in both cell lines at 2 μM.
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Cell Line:pediatric GBM cell line SJ-GBM2, diffuse intrinsic pontine glioma (DIPG) cell line SU-DIPG-VI
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Concentration:0.25 μM
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Incubation Time:2, 24 h
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Result:Showed a significant decrease in gap closure (cell motility) compared to vehicle-treated control cells at 24 h post-scratch.
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Cell Line:pediatric GBM cell line SJ-GBM2
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Concentration:1 μM, 2.5 μM
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Incubation Time:24 h
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Result:Increased phosphorylation of ERK1/2 and c-Jun.
Elevated expression of p53 and its downstream proapoptotic target PUMA.
Increased phosphorylation of histone H2AX (γ-H2AX), indicating activation of oxidative stress signaling, p53-mediated apoptosis, and DNA double-strand breaks.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:1, 2, 3 μM
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Incubation Time:4 days
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Result:Reduced MDA-MB-231 cell viability in a dose-dependent manner.
Left viability remaining above 60% at 2 μM.
Dropped viability to ~20% at 3 μM.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:0.25, 0.5, 1, 2 μM
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Incubation Time:8 h
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Result:Induced dose-dependent upregulation of HO1 mRNA.
Caused ~30-fold change at 0.5 μM.
Caused ~80-fold change at 1 μM.
Caused ~270-fold change at 2 μM.
Showed statistically significant increases compared to control at each dose.
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Cell Line:U87 glioma cells
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Concentration:1 μM (time-course); 1, 2, 3 μM (8 h incubation)
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Incubation Time:2 h, 4 h, 6 h, 16 h, 24 h (1 μM); 8 h (1-3 μM)
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Result:Caused a time-dependent decrease in Keap1 protein levels, with reductions visible as early as 4 h and restoration to baseline by 24 h.
Induced a dose-dependent decrease in Keap1 protein levels after 8 h of treatment, with the lowest levels detected at 3 μM.
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Cell Line:293T human embryonic kidney fibroblasts expressing HA-tagged Keap1
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Concentration:2 μM (obtusaquinone); 10 μM (MG132)
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Incubation Time:6 h
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Result:Induced ubiquitination of Keap1.
Increased the level of ubiquitinated Keap1 when cotreated with MG132.
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Cell Line:U87 glioma cells stably expressing nontargeting shRNA (shCtrl) or Keap1-targeting shRNA (shKeap1)
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Concentration:0.5, 1, 1.5, 2 μM
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Incubation Time:4 days
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Result:Reduced cell viability in a dose-dependent manner in shCtrl cells, with ~50% viability at 1 μM and ~10% viability at 2 μM.
Left viability remaining above 90% at 1 μM and ~75% at 2 μM in shKeap1 cells.
Showed statistically significant differences in viability between shCtrl and shKeap1 cells at 1 μM and 2 μM.
Obtusaquinone (0.75 mg/kg; intranasal administration; 3 times per week for 2 weeks) inhibits tumor growth of pediatric glioblastoma in orthotopic xenograft models via intranasal delivery and extends the median survival time of mice[1].
Obtusaquinone (OBT) (7.5 mg/kg; i.p.; once daily; for 4 consecutive days) activates the Nrf2 pathway in vivo, which is evidenced by the upregulated expression of HO1 mRNA in MDA-MB-231 breast cancer tumors of treated nude mice[2].
Obtusaquinone (10 mg/kg; administered three times within 24 h) can cross the blood-brain barrier, target orthotopic glioblastoma and exert functions in mice, thereby reducing the FDG uptake of tumors[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunodeficient mice (4-week-old, 50 000
SU-DIPG-VI cells (in small neurospheres))[1] -
Dosage:7.5 mg/kg
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Administration:i.p.; once daily; 3 days per week for 4 weeks
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Result:Reduced average firefly luciferase signal from brain tumors by 110 times relative to controls at day 55 post-implantation.
Extended median survival to 157 days compared to 100 days in controls.
Confirmed reduced tumor size via histological analysis.
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Animal Model:
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Dosage:0.75 mg/kg
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Administration:intranasal administration; 3 times per week for 2 weeks
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Result:Inhibitsed tumor growth of pediatric glioblastoma in orthotopic xenograft models via intranasal delivery and extends the median survival time of mice.
Chemical Information
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CAS No. 21105-15-7
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Molecular Weight 254.28
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Formula C16H14O3
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SMILES
COC(/C1=C/C=C/C2=CC=CC=C2)=CC(C(O)=C1)=O
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Structure Classification
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Initial Source
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Teng J, et al. The natural compound obtusaquinone targets pediatric high-grade gliomas through ROS-mediated ER stress. Neuro-oncology advances. 2020;2(1):vdaa106. [Content Brief]
[2]. Badr CE, et al. Obtusaquinone: A Cysteine-Modifying Compound That Targets Keap1 for Degradation. ACS chemical biology. 2020 Jun 19;15(6):1445-1454. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Obtusaquinone Related Classifications
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