Bt354
Bt354 is an orally active STAT3 inhibitor with IC50 values of 4.6 μM (DU145), 6.5 μM (MDA-MB-435) and 7.2 μM (MDA-MB-231), respectively. Bt354 induces cell cycle arrest and apoptosis, and downregulates epithelial-mesenchymal transition-related genes. Bt354 exhibits anti-angiogenic and anti-inflammatory activities, attenuates the polarization of M1 microglia and A1 astrocytes, suppresses inflammasome-related signaling pathways, and alleviates mechanical hyperalgesia and thermal hyperalgesia. Bt354 can be used in research related to glioblastoma multiforme, triple-negative breast cancer, prostate cancer and neuropathic pain.
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- No. CAS: 931305-29-2
- Fòrmula: C21H21N3O3S
- Peso molecular:395.48
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| DU-145 | IC50 |
0.12 μM
Compound: 2
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Antiproliferative activity against human DU-145 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human DU-145 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36511661] |
Bt354 (0.1-100 μM; 24-72 h) exhibits concentration- and time-dependent antiproliferative activity against U87 MG, GBM8401 and T98G glioblastoma cells, with IC50 values of 9.96 μM, 15.18 μM and 3.39 μM, respectively, after 24 h of incubation[1].
Bt354 (0.01-5 μM; 48 h) induces apoptosis in U87 MG glioblastoma cells in a concentration-dependent manner, and a significant increase in the proportion of apoptotic cells is observed at concentrations of 0.1 μM and above after 48 h of incubation[1].
Bt354 (0.1-5 μM; 24 h) induces apoptosis in U87 MG glioblastoma cells by upregulating the expression of cleaved caspase-3 and cleaved PARP, and reducing the activity of pro-caspase-3; a significant effect is observed at concentrations of 0.1 μM and above after 24 h of incubation[1].
Bt354 (0.1-5 μM; 24 h) inhibits epithelial-mesenchymal transition in U87 MG glioblastoma cells by upregulating E-cadherin expression and downregulating the expressions of vimentin, matrix metalloproteinase-2 (MMP-2), ZEB1 and FOXM1; after 24 h of incubation, significant effects are observed at concentrations of 0.1 μM and above (the effective concentrations for E-cadherin and ZEB1 are 1 μM and above)[1].
Bt354 (0.01-5 μM; 6-18 h) inhibits the migration of U87 MG glioblastoma cells in a concentration- and time-dependent manner. A significant migration-inhibiting effect is observed at concentrations of 0.01 μM and above, and the inhibitory effect reaches the maximum level after 18 h of incubation[1].
Bt354 (0.1-5 μM; 24 h) alters the polymerization state of F-actin in U87 MG glioblastoma cells, converting filamentous F-actin into a globular form near the nucleus; it inhibits cell migration after 24 h of incubation at concentrations of 0.1 μM and above[1].
Bt354 (0.1-5 μM; 24 h) regulates epithelial-mesenchymal transition in U87 MG glioblastoma cells by upregulating E-cadherin expression and downregulating vimentin expression, and this effect occurs at concentrations of 0.1 μM or higher after 24 h of incubation[1].
Bt354 (0.1-5 μM; 24 h) reduces the production of MMP-2 in U87 MG glioblastoma cells in a concentration-dependent manner in vitro, and a significant reduction is observed at concentrations of 0.1 μM and above after 24 h of incubation[1].
Bt354 (24 h) potently inhibits STAT3-dependent luciferase activity in DU145, MDA-MB-435 and MDA-MB-231 cells, with IC50 values of 4.6 μM, 6.5 μM and 7.2 μM, respectively[3].
Bt354 (24-72 h) inhibits the proliferation of DU145, MDA-MB-435 and MDA-MB-231 cells in a time- and dose-dependent manner, with its IC50 values ranging from 0.07 μM to 35 μM depending on the cell line and incubation time[3].
Bt354 specifically inhibits the phosphorylation of STAT3 at the Tyr705 site (without affecting phosphorylation at the Ser727 site or the upstream JAK2/Src signaling pathway), and downregulates the expression of STAT3-dependent pro-proliferative and anti-apoptotic proteins in MDA-MB-435 and MDA-MB-231 cells[3].
Bt354 (0.1-5 μM; 12 h) inhibits the nuclear translocation of STAT3 in MDA-MB-435 and MDA-MB-231 cells in a dose-dependent manner, which is evidenced by the reduced nuclear STAT3 levels after treatment with 1 μM or 5 μM Bt354 for 12 h[3].
Bt354 (0.5 μM; 24 h) induces G2/M cell cycle arrest in MDA-MB-435 and MDA-MB-231 cells[3].
Bt354 (48 h) induces late-stage apoptosis in MDA-MB-435 and MDA-MB-231 cells in a dose-dependent manner, increasing the proportion of late-stage apoptotic cells to 26.0% and 29.5%, respectively[3].
Bt354 (1 μM) inhibits the migration of MDA-MB-435 and MDA-MB-231 cells in a dose-dependent manner, with a significant inhibitory effect observed at the concentration of 1 μM in MDA-MB-435 cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U87 MG glioblastoma cells
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Concentration:0.01, 0.1, 1 and 5 μM
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Incubation Time:24 h; 48 h
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Result:Induced a significant, concentration-dependent increase in the proportion of apoptotic U87 MG cells at concentrations of 0.1 μM to 5 μM after 48 h treatment.
Showed no discernible apoptotic effect after 24 h of treatment at equivalent concentrations.
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Cell Line:U87 MG glioblastoma cells
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Concentration:0.1, 1 and 5 μM
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Incubation Time:24 h
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Result:Increased cleaved caspase-3 and cleaved PARP expression levels substantially at 1 μM.
Decreased pro-caspase-3 activity significantly in U87 MG cells treated with 0.1 μM and above.\nIncreased E-cadherin expression in a concentration-dependent manner, with significant increase observed at 1 μM and above.
Decreased vimentin, MMP-2, and FOXM1 expression in a concentration-dependent manner, with significant decreases observed at 0.1 μM and above.
Decreased ZEB1 expression in a concentration-dependent manner, with significant decrease observed at 1 μM and above.
Caused no significant changes in SLUG expression.
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Cell Line:U87 MG glioblastoma cells
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Concentration:0.01, 0.1, 1 and 5 μM
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Incubation Time:6 h; 12 h; 18 h
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Result:Significantly inhibited U87 MG cell migration in a concentration- and time-dependent manner, with significant inhibition observed at 0.01 μM and above.
Increased inhibition over time, with the maximal effect observed at 18 h.
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Cell Line:U87 MG glioblastoma cells
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Concentration:0.1, 1 and 5 μM
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Incubation Time:24 h
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Result:Altered F-actin polymerization in U87 MG glioblastoma cells, converting filamentous F-actin to a globular form near the nucleus.
Inhibited cell metastasis in treated cells.\nIncreased E-cadherin expression significantly as Bt354 concentration increased.
Decreased vimentin expression significantly with increasing Bt354 concentration.
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Cell Line:U87 MG glioblastoma cells
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Concentration:0.1, 1 and 5 μM
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Incubation Time:24 h
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Result:Reduced MMP-2 concentration in U87 MG cell supernatant in a concentration-dependent manner.
Showed significant effects at 0.1 μM and above.
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Cell Line:MDA-MB-435 human triple negative breast cancer cells, MDA-MB-231 human triple negative breast cancer cells
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Concentration:0.1, 1 and 5 μM
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Incubation Time:12 h
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Result:Reduced nuclear STAT3 levels substantially in a dose-dependent manner, with STAT3 remaining primarily in the cytoplasm after treatment with 1 μM or 5 μM Bt354 for 12 h.
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Cell Line:MDA-MB-435 human triple negative breast cancer cells, MDA-MB-231 human triple negative breast cancer cells
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Concentration:0.5 μM
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Incubation Time:24 h
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Result:Caused G2/M phase accumulation, with G2/M percentages increasing to 28.68% (MDA-MB-435) and 27.50% (MDA-MB-231).
Bt354 (10-40 mg/kg; p.o.; once every 3 days; 21 days) elicits dose-dependent antitumor activity in MDA-MB-231 xenograft mice[3].
Bt354 (10-40 mg/kg; p.o.; once every 3 days; 21 days) elicits dose-dependent antitumor activity in MDA-MB-435 xenograft mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wistar (adult male, 250-285 g, chronic constriction injury of right sciatic nerve, intrathecal catheter implantation prior to CCI induction)[2]
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Dosage:0.1-20 μg (acute testing); 0.25-1 μg/h (preventive testing)
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Administration:i.t.; single injection (acute testing); continuous infusion, 7-14 days (preventive testing)
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Result:Produced dose-dependent analgesic effect on CCI-induced thermal hyperalgesia with pharmacodynamic activity lasting up to 24 hours.
Calculated ED50 of 1.176 μg.
Resulted in significantly higher paw withdrawal threshold values than CCI + vehicle controls from day 3 to day 14 post-surgery.
Elevated paw withdrawal latency values relative to CCI + vehicle controls from day 1 to day 14 post-surgery, with dose-dependent improvement observed.
Significantly attenuated CCI-induced upregulation of STAT3 and phosphorylated STAT3 in the ipsilateral spinal cord dorsal horn, including reduced nuclear translocation of neuronal pSTAT3.
Mitigated CCI-induced activation and pro-inflammatory polarization of microglia and astrocytes.
Suppressed neuronal NLRP3 inflammasome expression.
Reduced neuronal LDHA and pTBK1 expression.
Attenuated microglial pCREB and pP38 expression.
Decreased pro-inflammatory cytokine production in neurons and microglia.
Inhibited CCI-induced angiogenesis.
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Animal Model:BalB/c-nu/nu (female, 8-10 week old)[3]
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Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg
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Administration:p.o.; once every 3 days; 21 days
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Result:Reduced mean tumor volume to 1303.2 mm3 (10 mg/kg), 976.0 mm3 (20 mg/kg), and 811.0 mm3 (40 mg/kg), compared to 2604.3 mm3 in controls.
Achieved tumor growth inhibition (T/C) values of 50%, 37.4%, and 31.3% for the 10, 20, and 40 mg/kg groups, respectively.
Decreased tumor weight by 74.6% in the 40 mg/kg group.
Reduced p-STAT3(Y705) levels in tumor tissue in a dose-dependent manner.
Lowered Ki-67-positive cell counts in all Bt354-treated groups.
Increased tumor cell apoptosis (measured via TUNEL assay) in a dose-dependent manner across all Bt354 groups.\nReduced mean tumor volume to 393.2 mm3 (10 mg/kg), 351.1 mm3 (20 mg/kg), and 321.4 mm3 (40 mg/kg), compared to 1365.8 mm3 in controls.
Achieved tumor growth inhibition (T/C) values of 28.7%, 25.7%, and 23.5% for the 10, 20, and 40 mg/kg groups, respectively.
Decreased tumor weight by 56.2%, 63.8%, and 77.1% in the 10, 20, and 40 mg/kg groups, respectively.
Reduced p-STAT3(Y705) levels in tumor tissue in a dose-dependent manner.
Lowered Ki-67-positive cell counts in all Bt354-treated groups.
Increased tumor cell apoptosis (measured via TUNEL assay) in a dose-dependent manner across all Bt354 groups.
Chemical Information
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No. CAS 931305-29-2
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Peso molecular 395.48
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Fòrmula C21H21N3O3S
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SMILES
O=C(NCC=1C=NC=CC1)C2=CC=C(C(=C2)NS(=O)(=O)C3=CC=C(C=C3)C)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Chiang YC, et al. STAT3 phosphorylation inhibitor Bt354 exhibits anti-neoplastic activity in glioblastoma multiforme cells. Environ Toxicol. 2024;39(6):3292-3303. [Content Brief]
[2]. Cheng HJ, et al. Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation. Neurotherapeutics. 2025;22(6):e00763. [Content Brief]
[3]. Chen Y, et al. Bt354 as a new STAT3 signaling pathway inhibitor against triple negative breast cancer. J Drug Target. 2018;26(10):920-930. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Bt354 Related Classifications
HY-155949 Related Classifications
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