PROTAC RNF4 degrader-1
PROTAC RNF4 degrader-1 is a RNF4 PROTAC degrader (Kd = 64.5 nM) that degrades RNF4 via the ubiquitin-proteasome system. PROTAC RNF4 degrader-1 induces DNA damage, apoptosis, and exhibits antiproliferative activity in cancer cells. PROTAC RNF4 degrader-1 displays antitumor activity with no obvious side effects in mouse models. PROTAC RNF4 degrader-1 is applicable to the research of hepatocellular carcinoma.
(Pink: RNF4 ligand (HY-143346); Blue: VHL ligand (HY-125845); Black: linker).
For research use only. We do not sell to patients.
- Formula: C47H52ClN5O7S
- Molecular Weight:866.46
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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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- References
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Biological Activity
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VHL |
RNF4 64.5 nM (Kd) |
PROTAC RNF4 degrader-1 (Compound RD12) (0.2-20 μM; 72 h) potently inhibits the proliferation of HepG2 human hepatocellular carcinoma cells with an IC50 of 0.48 μM[1].
PROTAC RNF4 degrader-1 (0.1-10 μM; 6 h) induces dose-dependent degradation of RNF4 protein in HepG2 human hepatocellular carcinoma cells[1].
PROTAC RNF4 degrader-1 (0-20 μM; 6 h) induces dose-dependent degradation of RNF4 protein in Huh7 human hepatocellular carcinoma cells with a DC50 of 4.16 μM[1].
PROTAC RNF4 degrader-1 (5 μM; 6 h after 2 h pre-incubation with MG132)-mediated RNF4 degradation in HepG2 and Huh7 human hepatocellular carcinoma cells is dependent on the ubiquitin-proteasome system, as pre-treatment with proteasome inhibitor MG132 reverses RNF4 loss[1].
PROTAC RNF4 degrader-1 (0.1-10 μM; 6 h) induces dose-dependent DNA damage in HepG2 and Huh7 human hepatocellular carcinoma cells, as measured by increased γH2AX levels[1].
PROTAC RNF4 degrader-1 (0-20 μM; 6 h) increases levels of RNF4 substrate proteins BRCA1 and MDC1 in a dose-dependent manner in Huh7 human hepatocellular carcinoma cells, consistent with RNF4 degradation[1].
PROTAC RNF4 degrader-1 (serial two-fold dilutions; 30 min at room temperature) binds directly to recombinant RNF4 protein with a Kd of 64.5 nM, as measured by MST[1].
PROTAC RNF4 degrader-1 (10 μM; 6 h) selectively induces degradation of RNF4 in Huh7 human hepatocellular carcinoma cells, with only 28 of 7483 identified proteins showing significant down-regulation[1].
PROTAC RNF4 degrader-1 (5 μM; 48 h) induces apoptosis in 52.1% of Huh7 human hepatocellular carcinoma cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2 human hepatocellular carcinoma cells
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Concentration:0.2, 2, 20 μM
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Incubation Time:72 h
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Result:Inhibited HepG2 cell proliferation with an IC50 of 0.48 ± 0.095 μM.
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Cell Line:HepG2 human hepatocellular carcinoma cells
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Concentration:0.1, 1.25, 2.5, 5, 10 μM
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Incubation Time:6 h
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Result:Induced dose-dependent degradation of RNF4 protein, with reduced RNF4 levels observed at all tested concentrations relative to untreated cells.
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Cell Line:Huh7 human hepatocellular carcinoma cells
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Concentration:0.1, 1.25, 2.5, 5, 10 μM; 0, 0.625, 1.25, 2.5, 5, 10, 20 μM
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Incubation Time:6 h
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Result:Induced dose-dependent degradation of RNF4 protein with a DC50 (degradation half-maximal concentration) of 4.16 ± 0.222 μM.
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Cell Line:HepG2 and Huh7 human hepatocellular carcinoma cells
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Concentration:5 μM
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Incubation Time:6 h (after 2 h pre-incubation with MG132)
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Result:Mediated RNF4 degradation that was rescued by pre-treatment with MG132, confirming dependency on the ubiquitin-proteasome system.
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Cell Line:HepG2 and Huh7 human hepatocellular carcinoma cells
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Concentration:0.1, 1.25, 2.5, 5, 10 μM
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Incubation Time:6 h
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Result:Induced dose-dependent increases in γH2AX levels (a marker of DNA double-strand breaks), with higher γH2AX expression observed at higher concentrations.
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Cell Line:Huh7 human hepatocellular carcinoma cells
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Concentration:0, 5, 10, 20 μM
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Incubation Time:6 h
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Result:Induced dose-dependent increases in BRCA1 and MDC1 protein levels (known substrates of RNF4), corresponding to reduced RNF4 levels.
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Cell Line:Huh7 human hepatocellular carcinoma cells
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Concentration:5 μM
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Incubation Time:48 h
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Result:Induced apoptosis in 52.1% of Huh7 cells, as measured by Annexin V staining.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (6-week-old, female, subcutaneously implanted with Huh7 cells)[1]
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Dosage:5 mg/kg; 20 mg/kg
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Administration:i.p.; once every two days; 20 days
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Result:Achieved tumor growth inhibition rates of 58% at 5 mg/kg and 76% at 20 mg/kg compared to vehicle controls.
Induced significant degradation of RNF4 protein in tumor tissues at 5 mg/kg.
Caused no significant changes in mouse body weight.
Resulted in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels similar to healthy controls, indicating no liver toxicity.
Chemical Information
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Molecular Weight 866.46
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Formula C47H52ClN5O7S
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SMILES
ClCC(N(CC1=CC=CC=C1)C(C=C2)=CC=C2OC(C=C3)=CC=C3OCCCC(N[C@H](C(N4C[C@@H](C[C@H]4C(NCC5=CC=C(C=C5)C6=C(N=CS6)C)=O)O)=O)C(C)(C)C)=O)=O
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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)
PROTAC RNF4 degrader-1 Related Classifications
HY-181692 Related Classifications
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