E722-2648
E722-2648 is an inhibitor targeting the BCL9 and β-catenin complex with antitumor activity. E722-2648 blocks complex formation by disrupting the interaction between the two proteins, thereby inhibiting β-catenin-mediated transcriptional activity and downregulating the expression of WNT target genes. E722-2648 effectively inhibits tumor growth in colon cancer xenograft models and colorectal cancer mouse models. E722-2648 can be used for the research of colon cancer and colorectal cancer.
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- CAS No.: 931963-55-2
- Formule: C21H30N2OS2
- Masse moléculaire:390.61
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
E722-2648 (1-20 μM; 16 h) dose-dependently inhibits the formation of endogenous β-catenin/BCL9 complexes in Colo320 and HCT116 colorectal cancer cells, without disrupting the interaction between β-catenin and E-cadherin, and exhibits excellent target specificity[1].
E722-2648 (6.25-25 μM; 16 h) dose-dependently inhibits the transcriptional activity of the Wnt/β-catenin pathway in dual-luciferase reporter assays using Colo320 and HCT116 colorectal cancer cells[1].
E722-2648 (10 μM, 20 μM; 6-48 h) downregulates the mRNA expression levels of Wnt pathway target genes AXIN2 and CD44 in a time- and dose-dependent manner in Colo320 and HCT116 colorectal cancer cells[1].
E722-2648 (25-50 μM; 24 h) dose-dependently downregulates the mRNA expression levels of Wnt pathway target genes AXIN2, CD44, and LGR5 in human neoplastic colon organoids carrying the APC gene c.4778delA mutation[1].
E722-2648 (5-20 μM; 24-48 h) dose-dependently downregulates the protein expression levels of AXIN2, CD44 and active β-catenin, and simultaneously increases the level of cleaved PARP to induce apoptosis in Colo320 and HCT116 colorectal cancer cells, whereas it exerts no such effects on β-catenin-independent RKO cells[1].
E722-2648 (20 μM; 48 h) significantly reduces the viability of HCT116 and Colo320 colorectal cancer cells. The decrease in cell viability becomes more pronounced when combined with the Wnt inhibitor ICG-001, the cholesterol synthesis inhibitor Lovastatin (HY-N0504), and the cholesterol esterification inhibitor Avasimibe (HY-13215). Exogenous cholesterol supplementation partially rescues the reduction in cell viability induced by E722-2648 treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human CRC cell lines Colo320, HCT116, DLD-1; murine breast cancer cell line 4T1
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Concentration:1 μM, 10 μM, 20 μM
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Incubation Time:16 h
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Result:Dose-dependently inhibited the formation of endogenous β-catenin/BCL9 complexes in Colo320 and HCT116 cells, with significant inhibitory effect observed at concentrations as low as 1 μM.
In DLD-1 cells with high E-cadherin expression, E722-2648 did not disrupt the interaction between β-catenin and E-cadherin at any tested concentration.
Also dose-dependently inhibited the binding of murine BCL9 to β-catenin in 4T1 cells.
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Cell Line:Human CRC cell lines Colo320, HCT116, RKO; neoplastic human colon organoids with APC c.4778delA mutation
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Concentration:5 μM, 10 μM, 20 μM (for CRC cell lines); 25 μM, 50 μM (for colon organoids)
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Incubation Time:24 h, 48 h, 72 h, 96 h (for CRC cell lines); 24 h, 48 h (for colon organoids)
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Result:Significantly reduced the proliferation of Colo320 and HCT116 cells in a time- and dose-dependent manner at all tested concentrations.
Had no inhibitory effect on the proliferation of the β-catenin-independent RKO cell line.
In neoplastic human colon organoids, E722-2648 dose-dependently inhibited proliferation and induced obvious apoptosis of organoids after 24 and 48 h of treatment.
E722-2648 (3 mg/kg; intratumoral injection; administered once every other day for 20 days) significantly inhibits subcutaneous tumor growth, reduces tumor weight and GFP fluorescence signals in tumor tissues, downregulates the expression of Wnt pathway target genes AXIN2 and CD44 in tumor tissues, suppresses tumor cell proliferation and tumor angiogenesis, induces tumor cell apoptosis, and decreases the infiltration of pro-tumor M2-like tumor-associated macrophages in the subcutaneous colorectal cancer xenograft model of NCr nude mice bearing HCT116-GFP cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD scid gamma (NSG) mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ, 5-week-old female), established with intraperitoneal colorectal cancer xenograft model via intraperitoneal injection of 2×106 HCT116 cells[1]
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Dosage:4 mg/kg
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Administration:Intraperitoneal injection every other day for 20 days
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Result:Significantly inhibited the growth of intraperitoneal colorectal tumors in NSG mice.
After 20 days of administration, Significantly lowered the weight and volume of the dissected tumors from treated mice than those from the vehicle control group.
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Animal Model:NCr nude mice (Taconic, 5-week-old female), established with subcutaneous colorectal cancer xenograft model via subcutaneous injection of 2×105 HCT116 cells stably expressing green fluorescent protein (GFP)[1]
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Dosage:3 mg/kg
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Administration:Intratumoral injection every other day for 20 days
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Result:Significantly suppressed the growth of subcutaneous HCT116 tumors in NCr nude mice, with a significant reduction in tumor volume, tumor weight, and GFP fluorescence intensity of tumor tissues compared with the vehicle control group.
Significantly downregulated the protein expression of Wnt target genes AXIN2 and CD44 in tumor tissues, decreased the expression of the proliferation marker Ki-67 and angiogenesis marker CD31, and increased the expression of the apoptosis marker cleaved caspase-3.
Significantly reduced the infiltration of protumorigenic M2-like tumor-associated macrophages marked by CD163 in tumor tissues.
Chemical Information
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CAS No. 931963-55-2
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Masse moléculaire 390.61
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Formule C21H30N2OS2
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SMILES
O=C(C1=CC(SC2=C3CCCC2)=C3CS1)NCCCN4CCCC(C4)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Groenewald W, et al. The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options. Cells. 2023;12(7):990. Published 2023 Mar 24. [Content Brief]
[2]. Cao M, et al. Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer. Curr Issues Mol Biol. 2022;44(10):4447-4471. Published 2022 Sep 26. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
E722-2648 Related Classifications
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