R4VPL3-1
R4VPL3-1 is a PROTAC-like degrader that simultaneously targets RNF4 and VHL, and also acts as a ferroptosis inducer. R4VPL3-1 induces iron-dependent lipid peroxidation and ferroptosis-mediated rapid cell death in cancer cells. R4VPL3-1 is applicable to research on human melanoma, human cutaneous squamous cell carcinoma, metastatic human sarcoma, malignant peripheral nerve sheath tumor, pigmented villonodular synovitis, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and lung adenocarcinoma.
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- Formule: C57H72ClN7O10S
- Masse moléculaire:1082.74
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Activité biologique
Description
IC50 & Target
[1]|
GPX4 |
VHL |
RNF4 |
In Vitro
R4VPL3-1 (5-10 μM; 2-6 h) induces dose- and time-dependent degradation of RNF4, its stabilized phosphorylated oncoprotein substrates (p-c-Myc, p-β-catenin), and VHL in PLX4032-resistant A375R human melanoma cells[1].
R4VPL3-1 (0.1-3 μM; 3-8 days) selectively inhibits proliferation and sphere formation of cancer cells (A375R, SCC1, 143B) but not non-tumorigenic HaCaT cells or primary MEFs, with IC50 values of ~0.3 μM for SCC1 cells and ~1.2 μM for A375R cells[1].
R4VPL3-1 (3 μM; 72 h) selectively inhibits proliferation of BEAS-2B cells transformed with EGFR pathway oncogenes (BRAFV600E, EGFR L858R) but not with a PI3K pathway oncogene (PIK3CA H1047R)[1].
R4VPL3-1 (1-10 μM; 2-6 h) induces time- and dose-dependent cell death in PLX4032-resistant A375R human melanoma cells, with >50% cell death observed at 3 μM after 6 h or at 10 μM after 4 h[1].
R4VPL3-1 (3 μM; 2-2.5 h) induces lipid peroxidation in PLX4032-resistant A375R human melanoma cells, a hallmark of ferroptosis, and this effect is blocked by the ferroptosis inhibitor Ferr-1 (HY-100579)[1].
R4VPL3-1 (0.1-5 μM; 3-8 days) inhibits proliferation and sphere formation of multiple primary patient-derived sarcoma and lung adenocarcinoma cells, with IC50 values ranging from 0.3 μM to 1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293 cells overexpressing HA-tagged wild-type RNF4 or HA-tagged RNF4 double mutant (HA-RNF4DM, Cys51A/Cys91A)
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Concentration:3 µM (Biotin-R4VPL3-1 binding)
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Incubation Time:48 h (post-transfection); 2 h (α-HA beads incubation); 1 h (Biotin-R4VPL3-1 binding at 4°C)
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Result:Bound to HA-RNF4, as detected by α-biotin Western blot.
Did not bind to HA-RNF4DM, which harbors mutations at Cys51 and Cys91.
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Cell Line:PLX4032-resistant A375R human melanoma cells
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Concentration:5-10 μM (dose-dependent treatment for RNF4, p-c-Myc, p-β-catenin; dose-dependent treatment for VHL); 10 μM (time-dependent treatment for RNF4, p-c-Myc, p-β-catenin; time-dependent treatment for VHL)
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Incubation Time:2-6 h (time-dependent treatment for RNF4, p-c-Myc, p-β-catenin); 2-4 h (time-dependent treatment for VHL)
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Result:Caused a dose-dependent reduction in RNF4, p-c-Myc, and p-β-catenin protein levels, with 10 μM reducing RNF4 to ~15%, p-c-Myc to ~10%, and p-β-catenin to ~10% of control levels.
Reduced RNF4 to ~65% at 2 h, ~40% at 4 h, and ~30% at 6 h of control levels via time-dependent treatment with 10 μM.
Caused a dose-dependent reduction in VHL protein levels, with 5 μM and 10 μM reducing VHL to ~30% of control levels.
Reduced VHL to ~60% at 2 h and ~30% at 4 h of control levels via time-dependent treatment with 10 μM.
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Cell Line:non-tumorigenic HaCaT human keratinocytes, primary mouse embryonic fibroblasts (MEFs), PLX4032-resistant A375R human melanoma cells, SCC1 human squamous skin carcinoma cells, 143B metastatic human sarcoma cells
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Concentration:0.1-3 μM
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Incubation Time:8 days (sphere formation assay); 3 days (cell viability assay)
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Result:Had no significant effect on sphere formation or viability of HaCaT cells and MEFs at concentrations up to 3 μM.
Inhibited viability and sphere formation of SCC1 cells with an IC50 of ~0.3 μM, reducing viability to <10% and sphere formation to <5% at 3 μM.
Inhibited viability and sphere formation of A375R cells with an IC50 of ~1.2 μM, reducing viability to ~20% and sphere formation to <5% at 3 μM.
Reduced viability of 143B cells to <20% and sphere formation to ~20% at 2 μM.
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Cell Line:BEAS-2B human tracheal epithelial cells transformed with BRAFV600E, EGFR L858R, or PIK3CA H1047R oncogenes
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Concentration:3 μM
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Incubation Time:72 h
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Result:Inhibited proliferation of BEAS-2B cells transformed with BRAFV600E or EGFR L858R (EGFR pathway mutations).
Did not inhibit proliferation of BEAS-2B cells transformed with PIK3CA H1047R (PI3K pathway mutation).
Chemical Information
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Masse moléculaire 1082.74
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Formule C57H72ClN7O10S
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SMILES
O=C([C@@H]1N(C([C@@H](C(C)(C)C)NC(CCOCCOCCC(NCCCCOC2=CC=C(OC3=CC=C(N(CC4=CC=C(N(C)C)C=C4)C(CCl)=O)C=C3)C=C2)=O)=O)=O)C[C@H](O)C1)NCC5=CC=C(C6=C(C)N=CS6)C=C5
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
R4VPL3-1 Related Classifications
HY-184506 Related Classifications
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