ODZ10117
ODZ10117 is a STAT3 and NLRP3 inhibitor with a human STAT3 SH2 domain IC50 of 7.5 μM. ODZ10117 binds to the STAT3 SH2 domain, suppressing tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity. ODZ10117 binds to NLRP3, impairs NEK7 interaction, prevents inflammasome formation, and inhibits caspase-1 and IL-1β cleavage.ODZ10117 reduces MSU (HY-B2130A)-induced IL-1β release, lowers LPS (HY-D1056)-induced sepsis mortality, and exhibits anti-inflammatory effects. ODZ10117 induces apoptosis, suppresses breast cancer cell migration and invasion, reduces tumor growth and lung metastasis, and extends survival in breast cancer models. ODZ10117 can be used for the research of Monosodium urate (HY-B2130A)-induced peritonitis, LPS-induced sepsis, breast cancer, glioblastoma, and Alzheimer's disease.
For research use only. We do not sell to patients.
- CAS No.: 1632152-27-2
- Formula: C10H5Cl5N2O2
- Molecular Weight:362.42
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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
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NLRP3 |
STAT3 7.5 μM (IC50) |
ODZ10117 (5-40 μM; 6 h) exhibits no significant cytotoxicity on mouse bone marrow-derived macrophages at concentrations up to 40 μM following 6-hour incubation[1].
ODZ10117 (5-20 μM; 1 h pretreatment) dose-dependently inhibits NLRP3 inflammasome-mediated IL-1β release and pyroptosis in LPS-primed mouse bone marrow-derived macrophages treated with ATP, nigericin, silica crystals, or imiquimod, with maximal inhibition at 20 μM[1].
ODZ10117 (5-20 μM; 1 h pretreatment) inhibits NLRP3 inflammasome activation in LPS-primed mouse bone marrow-derived macrophages by suppressing caspase-1, IL-1β, and GSDMD cleavage, without altering the expression levels of core inflammasome components[1].
ODZ10117 (5-20 μM; 1 h pretreatment) does not inhibit AIM2 or NLRC4 inflammasome activation in LPS-primed mouse bone marrow-derived macrophages, demonstrating specificity for NLRP3 inflammasomes[1].
ODZ10117 (5-20 μM; 1 h pretreatment) dose-dependently inhibits NLRP3 inflammasome-mediated ASC translocation, oligomerization, and speck formation in LPS-primed mouse bone marrow-derived macrophages, without affecting ASC dynamics in AIM2 or NLRC4 inflammasome activation[1].
ODZ10117 (20 μM) inhibits the interaction between NLRP3 and NEK7 in HEK293T cells overexpressing these proteins[1].
ODZ10117 (300-900 μM; 30 min incubation with lysates) directly binds to NLRP3 and STAT3 in LPS-primed J774A.1 cell lysates, as shown by dose-dependent protection from pronase degradation, with no binding to NEK7 or caspase-1[1].
ODZ10117 binds to the ADP binding pocket of the NLRP3 NACHT domain via multiple stabilizing interactions, with a binding energy of -7.7 kcal/mol[1].
ODZ10117 snugly fits into the phospho-tyrosine binding pocket of the STAT3 SH2 domain with a Glide docking score of −6.17 kcal/mol, demonstrating higher binding affinity than known STAT3 inhibitors S3I-201 (HY-15146) and STA-21 (HY-121482)[2].
ODZ10117 (40 μM; 24 h) inhibits tyrosine phosphorylation of STAT3 in multiple constitutively STAT3-activated human cancer cell lines including HDLM-2, MDA-MB-231, HepG2, and U87MG[2].
ODZ10117 (40 μM; 24 h) inhibits IL-6-induced tyrosine phosphorylation of STAT3 in human cancer cell lines including RPMI8226, MCF-7, and U251MG[2].
ODZ10117 (40 μM; 24 h) inhibits STAT3 homodimerization and tyrosine phosphorylation in transfected MDA-MB-231 breast cancer cells[2].
ODZ10117 (40 μM; 24 h) induces apoptosis in MDA-MB-231 breast cancer cells by activating caspase-3 and PARP cleavage, and downregulating anti-apoptotic proteins Bcl-2, Bcl-xL, Mcl-1, and survivin[2].
ODZ10117 (40 μM; 24 h) inhibits nuclear translocation of tyrosine-phosphorylated STAT3 in MDA-MB-231 breast cancer cells[2].
ODZ10117 (2.5-40 μM; 24 h) inhibits STAT3 transcriptional activity in MDA-MB-231/STAT3-Luc breast cancer cells with an IC50 of 7.5 μM after 24 h of incubation[2].
ODZ10117 (40 μM; 0.5-12 h) inhibits tyrosine phosphorylation of STAT3 in MDA-MB-231 and MDA-MB-468 breast cancer cells starting at 2 h post-treatment[2].
ODZ10117 (10-40 μM; 9 h) inhibits tyrosine phosphorylation of STAT3 in MDA-MB-231 and MDA-MB-468 breast cancer cells in a concentration-dependent manner, with significant inhibition at ≥20 μM after 9 h of incubation[2].
ODZ10117 (40 μM; 16 h) specifically inhibits tyrosine phosphorylation of STAT3 without affecting other STAT family proteins, JAK kinases, or upstream signaling regulators Akt, Src, and ERK1/2 in MDA-MB-231 and MDA-MB-468 breast cancer cells[2].
ODZ10117 (10-100 μM; 24 h) reduces cell viability in MDA-MB-231, MDA-MB-468, ZR-75-1, and 4T1 breast cancer cells in a concentration-dependent manner after 24 h of incubation[2].
ODZ10117 (40 μM; 24 h) increases apoptotic cell death in MDA-MB-231 breast cancer cells, as shown by a five-fold increase in Annexin V-positive cells and a three-fold increase in PI-positive cells[2].
ODZ10117 (40 μM; 24 h) downregulates mRNA expression of STAT3-dependent anti-apoptotic genes Bcl-2, Bcl-xL, Mcl-1, and Survivin in MDA-MB-231 breast cancer cells[2].
ODZ10117 (40 μM; 24 h) reduces migration of MDA-MB-231 breast cancer cells in a wound healing assay[2].
ODZ10117 potently and selectively inhibits STAT3 transcriptional activity in breast cancer cells with an IC50 of 7.5 μM[3].
ODZ10117 exerts anticancer effects against MDA-MB-231 breast cancer cells by directly blocking the STAT3 SH2 domain, suppressing homodimerization and transcriptional activity, inducing apoptosis, and reducing migration and invasion[3].
ODZ10117 (10 μM; 12 h pretreatment) enhances cell viability in H2O2-treated SH-SY5Y human neuroblastoma cells by mitigating oxidative stress-induced cell damage[4].
ODZ10117 (10 μM; 12 h pretreatment) suppresses H2O2-induced caspase-dependent apoptosis in SH-SY5Y human neuroblastoma cells[4].
ODZ10117 (10 μM; 1-12 h) suppresses STAT3 phosphorylation and induces transient ERK and CREB phosphorylation in SH-SY5Y human neuroblastoma cells, with peak effects at 1 h[4].
ODZ10117 (10 μM; 1-12 h) upregulates protein expression of memory-associated IEGs and BDNF in SH-SY5Y human neuroblastoma cells, with detectable increases starting at 6 h[4].
ODZ10117 (10 μM; 3 h)-induced CREB phosphorylation in SH-SY5Y human neuroblastoma cells is dependent on ERK signaling[4].
ODZ10117 (10 μM; 3-6 h) upregulates mRNA expression of memory-associated IEGs in SH-SY5Y human neuroblastoma cells, with peak effects at 3 h[4].
ODZ10117 (10 μM; 12 h)-induced upregulation of memory-associated IEG and BDNF proteins in SH-SY5Y human neuroblastoma cells is dependent on ERK signaling[4].
ODZ10117 (10 μM; 12 h treatment) mitigates H2O2-induced oxidative stress and caspase-dependent apoptosis in SH-SY5Y human neuroblastoma cells is dependent on ERK signaling[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:mouse bone marrow-derived macrophages (BMDMs)
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Concentration:5 μM; 10 μM; 20 μM; 40 μM
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Incubation Time:6 h
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Result:Showed no significant cytotoxicity on BMDMs at concentrations up to 40 μM, with cell viability remaining near 100% across all tested concentrations.
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Cell Line:LPS-primed mouse bone marrow-derived macrophages (BMDMs)
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Concentration:5 μM; 10 μM; 20 μM
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Incubation Time:1 h pretreatment
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Result:Dose-dependently inhibited the cleavage of pro-caspase-1 to active caspase-1 (p20), pro-IL-1β to active IL-1β (p17), and full-length GSDMD to N-terminal GSDMD (N-GSDMD) in cell supernatants and lysates.
Had no effect on the steady-state protein levels of NLRP3, ASC, pro-caspase-1, pro-IL-1β, or full-length GSDMD in cell lysates.
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Cell Line:LPS-primed mouse bone marrow-derived macrophages (BMDMs)
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Concentration:5 μM; 10 μM; 20 μM
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Incubation Time:1 h pretreatment
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Result:Dose-dependently suppressed ASC translocation to Triton X-100 insoluble fractions, ASC oligomerization, and ASC speck formation in BMDMs treated with NLRP3 triggers (ATP, nigericin, silica crystals).
Reduced ASC speck formation by ~50% for ATP and nigericin triggers at 20 μM.
Had no effect on ASC translocation or speck formation in BMDMs treated with AIM2 or NLRC4 triggers.
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Cell Line:HDLM-2, L540, K562, KCL22, LAMA84, DU145, MDA-MB-231, MDA-MB-468, SKOV3, PANC-1, A549, NCI-H460, HCT116, SW620, MKN-45, A431, A375, SK-MEL-146, HepG2, Huh7, A172, U87MG, U373MG, SH-SY5Y
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Concentration:40 μM
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Incubation Time:24 h
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Result:Reduced the level of tyrosine-phosphorylated STAT3 in all tested constitutively STAT3-activated human cancer cell lines, without altering total STAT3 levels.
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Cell Line:RPMI8226, U266, U937, HL-60, HeLa, MCF-7, U251MG
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Concentration:40 μM
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Incubation Time:24 h
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Result:Reduced the level of tyrosine-phosphorylated STAT3 induced by IL-6 stimulation in all tested human cancer cell lines, without altering total STAT3 levels.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:40 μM
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Incubation Time:24 h
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Result:Decreased the level of tyrosine-phosphorylated STAT3 without altering total STAT3 levels, and significantly reduced STAT3 homodimerization compared to vehicle-treated cells.\nIncreased the levels of cleaved PARP and cleaved caspase-3, and reduced the protein levels of anti-apoptotic genes Bcl-2, Bcl-xL, Mcl-1, and Survivin compared to vehicle-treated cells.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:40 μM
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Incubation Time:24 h
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Result:Reduced the nuclear accumulation of tyrosine-phosphorylated STAT3 compared to vehicle-treated cells, where phosphorylated STAT3 was prominently localized in the nucleus.
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Cell Line:MDA-MB-231 and MDA-MB-468 breast cancer cells
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Concentration:40 μM
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Incubation Time:0.5 h; 1 h; 2 h; 4 h; 6 h; 9 h; 12 h
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Result:Reduced tyrosine-phosphorylated STAT3 levels after 2 h of incubation, with the inhibitory effect sustained through 12 h of treatment, without altering total STAT3 levels.
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Cell Line:MDA-MB-231 and MDA-MB-468 breast cancer cells
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Concentration:10 μM; 20 μM; 30 μM; 40 μM
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Incubation Time:9 h
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Result:Reduced tyrosine-phosphorylated STAT3 levels in a concentration-dependent manner, with significant inhibition observed at concentrations ≥20 μM, without altering total STAT3 levels.
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Cell Line:MDA-MB-231 and MDA-MB-468 breast cancer cells
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Concentration:40 μM
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Incubation Time:16 h
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Result:Inhibited tyrosine phosphorylation of STAT3, but did not significantly affect phosphorylation levels of STAT1, STAT5, JAK1, JAK2, JAK3, Akt, Src, or ERK1/2, nor did it alter total levels of any of these proteins.
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Cell Line:MDA-MB-231, MDA-MB-468, ZR-75-1, and 4T1 breast cancer cells
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Concentration:10 μM; 20 μM; 40 μM; 60 μM; 80 μM; 100 μM
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Incubation Time:24 h
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Result:Decreased cell viability in a concentration-dependent manner across all tested breast cancer cell lines.
At 100 μM, cell survival was reduced to 30-50% of vehicle-treated controls.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:40 μM
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Incubation Time:24 h
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Result:Increased the population of PI-positive dead cells from 7.86% to 26.7% and Annexin V-positive apoptotic cells from 3.13% to 15.3% compared to vehicle-treated cells.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:40 μM
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Incubation Time:24 h
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Result:Reduced the mRNA levels of Bcl-2, Bcl-xL, Mcl-1, and Survivin to 20-40% of vehicle-treated control levels.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:40 μM
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Incubation Time:24 h
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Result:Significantly reduced wound closure compared to vehicle-treated cells, indicating decreased cell migration.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h pretreatment
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Result:Significantly increased cell viability in SH-SY5Y cells exposed to H2O2, reversing the ~50% reduction in viability caused by H2O2 alone (statistically significant compared to the H2O2-treated group, p<0.005).
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h pretreatment
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Result:Significantly reduced the total green object area (a measure of dead cell cytotoxicity) in SH-SY5Y cells exposed to H2O2, compared to the H2O2-only group (p<0.005).
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h (pretreatment); 12 h (H2O2 exposure)
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Result:Significantly reduced the percentage of Annexin V-positive apoptotic SH-SY5Y cells exposed to H2O2, compared to the H2O2-only group (p<0.005).
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h pretreatment
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Result:Reduced H2O2-induced cleavage of caspase-3, caspase-9, and PARP in SH-SY5Y cells, indicating inhibition of caspase-dependent apoptosis.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:1 h; 3 h; 6 h; 12 h
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Result:Induced peak p-STAT3 suppression at 1 h (persisting until 6 h), peak p-CREB levels at 1 h (gradually declining thereafter), and peak p-ERK levels at 1 or 3 h (gradually declining until 12 h) in SH-SY5Y cells.\nSignificantly increased protein levels of c-Fos, c-Jun, and BDNF in SH-SY5Y cells starting at 6 h.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:3 h
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Result:Pretreatment with PD98059 significantly reduced ODZ10117-induced p-ERK and p-CREB levels in SH-SY5Y cells.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:3 h; 6 h
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Result:Significantly increased mRNA levels of all tested immediate early genes (c-Fos, c-Jun, Arc, Egr-1, NR4A1, and Homer1a) in SH-SY5Y cells, with a more pronounced response observed at 3 h compared to 6 h.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h
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Result:Induced increases in c-Fos, c-Jun, and BDNF protein levels in SH-SY5Y cells were abolished with PD98059 pretreatment.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h
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Result:Reduction of cell viability was reversed in H2O2-treated SH-SY5Y cells with PD98059 pretreatment.
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Cell Line:human neuroblastoma SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:12 h
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Result:Reduction in cytotoxicity, caspase-3, caspase-9, PARP cleavage and apoptotic cell rate was reversed in H2O2-treated SH-SY5Y cells with PD98059 pretreatment.
ODZ10117 (5-20 mg/kg; i.p.; two doses (12 h and 2 h prior to LPS)) dose-dependently reduces IL-1β release and improves survival rate in mice with LPS-induced sepsis, with significant efficacy observed at 10 and 20 mg/kg[1].
ODZ10117 (1-10 mg/kg; i.p.; 5 times per week; 23 days) suppresses orthotopic breast tumor growth in BALB/c nude mice in a dose-dependent manner, with the 10 mg/kg dose achieving greater tumor weight reduction than the 1 mg/kg dose[2].
ODZ10117 (10 mg/kg; intratumoral injection; every 2 days; 2 weeks) suppresses subcutaneous breast tumor growth in BALB/c nude mice and modulates STAT3-dependent apoptotic and metastatic markers in tumor tissue[2].
ODZ10117 (1-10 mg/kg; i.p.; 5 times per week; 3 weeks) suppresses primary tumor growth, reduces lung metastasis, and extends survival in a syngeneic breast cancer model in BALB/c mice, with the 10 mg/kg dose achieving greater efficacy than the 1 mg/kg dose[2].
ODZ10117 (10 mg/kg; intratumoral injection) significantly reduces tumor growth and lung metastasis in BALB/c mice with MDA-MB-231 breast cancer xenografts[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 6-8 weeks old, intraperitoneal injection of MSU crystals at 50 mg/kg)[1]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:i.p.; single dose
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Result:Suppressed MSU-induced IL-1β release in a dose-dependent manner.
Achieved statistically significant reductions in IL-1β levels at 10 mg/kg and 20 mg/kg (p < 0.01) compared to the MSU-only group.
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Animal Model:C57BL/6 (female, 6-8 weeks old, intraperitoneal injection of LPS at 20 mg/kg)[1]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:i.p.; two doses (12 h and 2 h prior to LPS)
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Result:Suppressed LPS-induced IL-1β release in a dose-dependent manner.
Achieved statistically significant reductions in IL-1β levels at 10 mg/kg and 20 mg/kg (p < 0.05) compared to the LPS-only group.
Improved survival rate: maintained 60% survival through 80 hours at 20 mg/kg, compared to 0% survival for the LPS-only group by 36 hours, with a statistically significant difference (p < 0.05).
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Animal Model:BALB/c nude (6-week-old female, orthotopic xenograft via MDA-MB-231 cell injection into right fourth mammary fat pad)[2]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:i.p.; 5 times per week; 23 days
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Result:Reduced final tumor weight to ~1.8 g (1 mg/kg dose) compared to vehicle control ~2.4 g.
Suppressed tumor volume growth over 22 days (1 mg/kg dose).
Reduced final tumor weight to ~1.4 g (10 mg/kg dose).
Suppressed tumor volume growth to a greater degree than the 1 mg/kg dose (10 mg/kg dose).
Did not affect mouse body weight (both doses).
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Animal Model:BALB/c nude (6-week-old female, subcutaneous xenograft via MDA-MB-231 cell injection into neck)[2]
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Dosage:10 mg/kg
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Administration:intratumoral injection; every 2 days; 2 weeks
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Result:Significantly suppressed relative tumor volume growth over 14 days, with final relative volume ~2 compared to vehicle control ~5.
Reduced tumor cell population in treated tumors.
Decreased levels of pY705-STAT3, Bcl-xL, and pro-MMP-2 in treated tumors.
Increased levels of active caspase-3 in treated tumors.
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Animal Model:BALB/c (6-week-old female, syngeneic xenograft via 4T1-Luc cell injection into right fourth mammary fat pad, spontaneous lung metastasis)[2]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:i.p.; 5 times per week; 3 weeks
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Result:Reduced primary tumor volume at 21 days (1 mg/kg dose).
Increased median mouse survival from 12 days to 20 days (1 mg/kg dose).
Reduced visible lung metastatic nodules to ~22 compared to vehicle control ~30 (1 mg/kg dose).
Reduced primary tumor volume to a greater degree than the 1 mg/kg dose (10 mg/kg dose).
Increased median survival to 21 days (10 mg/kg dose).
Reduced visible lung metastatic nodules to ~17 (10 mg/kg dose).
Did not affect mouse body weight (both doses).
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Animal Model:BALB/c[3]
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Dosage:10 mg/kg
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Administration:intratumoral injection
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Result:Significantly reduced tumor growth and lung metastasis.
Chemical Information
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CAS No. 1632152-27-2
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Molecular Weight 362.42
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Formula C10H5Cl5N2O2
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SMILES
ClC1=CC=C(C(Cl)=C1)OCC2=NOC(C(Cl)(Cl)Cl)=N2
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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]. Kang JH, et al. Novel Activity of ODZ10117, a STAT3 Inhibitor, for Regulation of NLRP3 Inflammasome Activation. Int J Mol Sci. 2023;24(7):6079. Published 2023 Mar 23. [Content Brief]
[2]. Kim BH, et al. Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy. J Clin Med. 2019;8(11):1847. Published 2019 Nov 2. [Content Brief]
[3]. Dong J, et al. Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation. J Med Chem. 2021;64(13):8884-8915. [Content Brief]
[4]. Kim SK, et al. Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway. Neurochem Res. 2024;50(1):52. Published 2024 Dec 9. [Content Brief]
Calculators
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