SNX631
SNX631 is an orally active and selective CDK8/CDK19 inhibitor. SNX631 reduces the phosphorylation of STAT1/STAT3 S727, and upregulates miR-21-5p, miR-21-3p and miR-221 in cancer cells. SNX631 transcription-independently inhibits meiotic resumption in mouse oocytes, blocks nuclear envelope breakdown, first polar body extrusion and mitochondrial expansion and aggregation, with no cytotoxicity. The combination of SNX631 with Lapatinib (HY-50898) or Trastuzumab (HY-P9907) synergistically inhibits cancer cell growth, upregulates the tumor suppressor BTG2 and prevents Lapatinib-induced upregulation of oncogenic miRNAs. SNX631 partially inhibits tumor growth; when combined with Lapatinib, it significantly suppresses tumors and overcomes drug resistance, reduces the infiltration of αSMA+ stromal fibroblasts and ARG1+ M2 macrophages, and exhibits favorable biosafety. SNX631 can be used in studies related to HER2-positive breast cancer and cancer.
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- No. CAS: 868066-26-6
- Fòrmula: C22H26N6O2S
- Peso molecular:438.55
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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CDK8 |
CDK19 |
STAT1 |
p-STAT3 |
SNX631 (0.01-1 μM; 7 days) synergistically enhances the growth-inhibitory effects of lapatinib and trastuzumab in HER2+ breast cancer cell lines (HCC1954-Par, HCC1954-Res, JIMT-1, SKBR3, BT474), with combination index values ranging from 0.011 to 0.645 for lapatinib combinations and 0.381 to 0.562 for trastuzumab combinations[1].
SNX631 (0.01-1 μM; 7 days) has its synergistic growth-inhibitory interaction with lapatinib abrogated by PI3K pathway inhibition in HCC1954-Par, HCC1954-Res, and JIMT-1 HER2+ breast cancer cell lines, with combination index values ranging from 0.919 to 1.744[1].
SNX631 (500 nM; 6 h) inhibits phosphorylation of STAT1 at S727 and STAT3 at S727 in HCC1954-Par, HCC1954-Res, and JIMT-1 HER2+ breast cancer cell lines, and this inhibitory effect is enhanced when combined with lapatinib or trastuzumab[1].
SNX631 (0.01-1 μM; 7 days) has reduced growth-inhibitory activity against HCC1954-Par HER2+ breast cancer cells with BTG2 knockdown[1].
SNX631 (0.01-1 μM; 7 days) has slightly enhanced growth-inhibitory activity against HCC1954-Par HER2+ breast cancer cells with double knockout of STAT1 and STAT3, but shows no change in activity against JIMT-1 cells with the same knockout[1].
SNX631 (0.5-1.5 μM; 1-4 h) does not alter phosphorylation of PKA or ERK1/2 in mouse embryonic fibroblasts after 1 hour or 4 hours 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:HER2+ breast cancer cell lines (HCC1954-Par, HCC1954-Res, JIMT-1)
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Concentration:500 nM
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Incubation Time:6 h
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Result:Decreased STAT1 S727 phosphorylation in all three cell lines.
Reduced STAT1 S727 phosphorylation to a greater extent when combined with lapatinib.
Enhanced reduction of STAT1 S727 phosphorylation when combined with trastuzumab compared to use alone.
Decreased STAT3 S727 phosphorylation (to a lesser extent than STAT1 phosphorylation) in all three cell lines.
Reduced STAT3 S727 phosphorylation to a greater extent when combined with lapatinib.
Enhanced reduction of STAT3 S727 phosphorylation in HCC1954-Res cells when combined with trastuzumab.
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Cell Line:mouse embryonic fibroblasts (MEFs)
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Concentration:0.5 μM, 1.5 μM
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Incubation Time:1 h, 4 h
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Result:Had no effect on phosphorylation levels of ERK1/2 or PKA in MEFs after 1 hour incubation at 0.5 μM or 1.5 μM.
Had no effect on phosphorylation levels of ERK1/2 or PKA in MEFs after 4 hours incubation at 0.5 μM or 1.5 μM.
Had no effect on total ERK1/2 levels in MEFs after 1 hour or 4 hours incubation at 0.5 μM or 1.5 μM.
SNX631 (250 ppm; medicated diet; continuous) plus (5 mg/kg; oral gavage; daily) alone significantly reduces tumor growth in lapatinib-resistant HER2+ breast cancer xenografts, with no apparent toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) (female, 6 weeks old)[1]
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Dosage:500 ppm
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Administration:medicated diet; continuous
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Result:Significantly decreased tumor size and final tumor weights compared to vehicle control.
Strongly decreased tumor proliferation measured by Ki67 staining.
Significantly decreased the ratio of phosphorylated STAT1 S727 to total STAT1.
Strongly decreased Arginase-1 (ARG1) staining, a marker of M2 macrophages.
Showed no treatment-related toxicity based on mouse body weights.
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Animal Model:NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) (female, 6 weeks old)[1]
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Dosage:250 ppm (medicated diet); 5 mg/kg (oral gavage)
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Administration:medicated diet; continuous; oral gavage; daily
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Result:Significantly decreased tumor size and final tumor weights compared to vehicle control.
Showed no treatment-related toxicity based on mouse body weights.
Chemical Information
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No. CAS 868066-26-6
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Peso molecular 438.55
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Fòrmula C22H26N6O2S
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SMILES
O=C(N)C=1SC2=NC=CC(=C2C1N)N3CCN(C4=CC=C(C=C4)C(=O)N(C)C)CCC3
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SNX631 Related Classifications
HY-187035 Related Classifications
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