FJ9
FJ9 is a NHERF1/PDZ inhibitor with human NHERF1 PDZ1 IC50 1540 μM, NHERF1 PDZ2 IC50 160 μM, and Frizzled-7-Dishevelled PDZ complex Ki 10 μM. FJ9 binds ligand-binding pockets of NHERF1 PDZ domains to block cognate ligand interactions, disrupts Frizzled-7-Dishevelled interactions, and down-regulates canonical Wnt signaling. FJ9 induces apoptosis in cancer cells with intact β-catenin signaling. FJ9 can be used for the research of non-small cell lung cancer, melanoma.
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- No. CAS: 873841-43-1
- Fòrmula: C23H27NO3
- Peso molecular:365.47
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Almacenamiento:
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Actividad biológica
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Chemical Information
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- Referencias
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Help & FAQs
Actividad biológica
FJ9 (Compound 1) inhibits the interaction between GST-fused human NHERF1 PDZ1 domain and biotinylated β2AR carboxy-terminal peptide with an IC50 of 1540 μM[1].
FJ9 inhibits the interaction between GST-fused human NHERF1 PDZ2 domain and biotinylated CFTR carboxy-terminal peptide with an IC50 of 160 μM[1].
FJ9 (0.1-1000 μM) competitively inhibits Frz7 peptide binding to purified human DVL1 PDZ domain with a Ki of 63 μM and to purified human DVL3 PDZ domain with a Ki of 29 μM[2].
FJ9 (100-300 μM; 24 hours) penetrates HEK293T cells and disrupts the intracellular interaction between HA-tagged mouse DVL1 and myc-tagged human Frz7 at concentrations of 100 μM and 300 μM[2].
FJ9 (100-300 μM; 48 hours) dose-dependently down-regulates cytosolic β-catenin levels in hTERT-immortalized LP9 mesothelial cells stably expressing full-length mouse DVL1, but not in control LP9 cells or LP9 cells expressing PDZ domain-deleted mouse DVL1[2].
FJ9 (100-300 μM; 24 hours) dose-dependently inhibits constitutive Tcf transcriptional activity in HCT116 p53-/- colon cancer cells, reducing TOPflash reporter activity while minimally affecting FOPflash reporter activity[2].
FJ9 (30-100 μM; 1-2 days) down-regulates canonical Wnt signaling target proteins (cyclin D1, c-myc, survivin) and mRNA (cyclin D1, survivin) in HCT116 p53-/- colon cancer cells, and down-regulates survivin protein in NCI-H1703 non-small cell lung cancer cells[2].
FJ9 (30-100 μM; 24 hours) does not affect JNK activation in mDVL1-transfected HeLa cells after 24 hours of treatment at 30 μM and 100 μM[2].
FJ9 (86-100 μM; 3 to 6 days) induces significant apoptosis in LOX melanoma, NCI-H460 non-small cell lung cancer, and NCI-H1703 non-small cell lung cancer cells, but has no apoptotic effect on NCI-H28 mesothelioma cells or normal NHBE and SAEC cells, after 3 to 6 days of treatment at 86 to 100 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T cells transiently expressing HA-tagged mouse DVL1 and myc-tagged human Frz7
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Concentration:100 μM; 300 μM
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Incubation Time:24 h
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Result:Diminished the formation of the intracellular DVL1-Frz7 complex at concentrations above the in vitro Ki value, as shown by reduced detection of myc-tagged Frz7 in anti-HA immunoprecipitates.
Left whole lysate myc-hFrz7 levels consistent.
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Cell Line:hTERT-immortalized LP9 mesothelial cells stably expressing empty vector, full-length mouse DVL1, or PDZ domain-deleted mouse DVL1 (ΔPDZ-DVL1)
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Concentration:100 μM; 300 μM
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Incubation Time:48 hours
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Result:Causes a dose-dependent down-regulation of cytosolic β-catenin exclusively in LP9 cells stably expressing full-length DVL1.
Causes no significant change in cytosolic β-catenin levels in control empty vector-expressing cells or ΔPDZ-DVL1-expressing cells.
Causes no significant cell death or morphologic changes in any cell line.
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Cell Line:HCT116 p53-/- colon cancer cells; NCI-H1703 non-small cell lung cancer cells
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Concentration:30 μM; 100 μM
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Incubation Time:2 days
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Result:Down-regulated canonical Wnt signaling target proteins (cyclin D1, c-myc, survivin) in HCT116 p53-/- colon cancer cells, and down-regulated survivin protein in NCI-H1703 non-small cell lung cancer cells
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Cell Line:HCT116 p53-/- colon cancer cells; NCI-H1703 non-small cell lung cancer cells
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Concentration:30 μM; 100 μM
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Incubation Time:1 day
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Result:Down-regulated cyclin D1 and survivin in HCT116 p53-/- colon cancer cells.
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Cell Line:HeLa cells transiently transfected with mouse DVL1
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Concentration:30 μM; 100 μM
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Incubation Time:24 hours
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Result:Has no effect on the dual phosphorylation (activation) of JNK in mDVL1-transfected HeLa cells, indicating no impact on non-canonical Wnt signaling mediated by JNK.
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Cell Line:LOX melanoma cells, NCI-H460 non-small cell lung cancer cells, NCI-H1703 non-small cell lung cancer cells, NCI-H28 mesothelioma cells, normal human bronchial epithelial (NHBE) cells, normal human small airway epithelial (SAEC) cells
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Concentration:86 μM; 100 μM
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Incubation Time:3 days; 4 days
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Result:Induces significant apoptosis in LOX, H460, and H1703 tumor cells with intact β-catenin signaling.
Neither suppresses growth nor induces apoptosis in H28 mesothelioma cells with a homozygous β-catenin gene deletion.
Has minimal effect on normal NHBE and SAEC cells which do not express Wnt-1.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSWNU-M (6-week-old female, injected s.c. with 4 million H460 tumor cells)[2]
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Dosage:50 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Significantly inhibited growth of H460 tumor xenografts.
Reduced mean tumor volume to ~300 mm3 on day 12 (vs ~400 mm3 for vehicle control).
Reduced mean tumor volume to ~275 mm3 on day 14 (vs ~475 mm3 for vehicle control).
Reduced mean tumor volume to ~325 mm3 on day 16 (vs ~700 mm3 for vehicle control).
Caused no significant mouse weight loss (<5%).
Chemical Information
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No. CAS 873841-43-1
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Peso molecular 365.47
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Fòrmula C23H27NO3
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SMILES
O=C(C1=CC2=C(NC(C(CCCC)O)=C2CCC3=CC=CC=C3)C=C1C)O
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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]. Mayasundari A, et al. Rational design of the first small-molecule antagonists of NHERF1/EBP50 PDZ domains. Bioorg Med Chem Lett. 2008;18(3):942-945. [Content Brief]
[2]. Fujii N, et al. An antagonist of dishevelled protein-protein interaction suppresses beta-catenin-dependent tumor cell growth. Cancer Res. 2007;67(2):573-579. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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