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.
For research use only. We do not sell to patients.
- Formula: C57H72ClN7O10S
- Molecular Weight:1082.74
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Storage:
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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Biological Activity
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Chemical Information
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Biological Activity
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GPX4 |
VHL |
RNF4 |
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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Molecular Weight 1082.74
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
R4VPL3-1 Related Classifications
HY-184506 Related Classifications
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