PROTAC MDM2 Degrader-8
PROTAC MDM2 Degrader-8 is a PROTAC degrader that induces the degradation of the MDM2 protein by recruiting VHL. PROTAC MDM2 Degrader-8 directly binds to MDM2 with a KD of 38.2 μM; the proteasome inhibitor MG-132 (HY-13259) reverses this degradation effect, supporting that it induces MDM2 degradation via the ubiquitin-proteasome system. PROTAC MDM2 Degrader-8 also upregulates p21, induces apoptosis and cell cycle arrest, and inhibits the migration of MDA-MB-231 cells. PROTAC MDM2 Degrader-8 can be used in studies related to MDM2-targeted protein degradation and triple-negative breast cancer.
(Pink: MDM-2/p53 and MDM-2 ligand (HY-N1447); Blue: VHL ligand (HY-112078); Black: linker).
For research use only. We do not sell to patients.
- Formula: C70H106N8O14S
- Molecular Weight:1315.70
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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
Description
IC50 & Target
[1]|
MDM2 38.2 μM (Kd) |
In Vitro
The cell viability of PROTAC MDM2 Degrader-8 (compound V10) (100 μM) in MCF-7, MDA-MB-231, SJSA-1, HepG2, and HT-22 cells is 30.6%, 16.9%, 61.3%, 92.9%, and 91.3% of that in the control group, respectively; among these, the proliferation inhibition rate in MDA-MB-231 cells is 83.1%[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces MDM2 protein levels in a concentration-dependent manner in p53-mutant MDA-MB-231 cells, with a maximum MDM2 degradation rate of 51% at 80 μM[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces the BCL-2/BAX ratio in MDA-MB-231 cells[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) inhibits the migration of MDA-MB-231 cells; at 80 μM, the migration inhibition rates at 24 h and 48 h are 55% and 69%, respectively[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) upregulates p21 protein levels concomitant with the reduction of MDM2 in MDA-MB-231 cells[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) upregulates p21 mRNA and reduces Cyclin B1 protein expression in MDA-MB-231 cells[1].
PROTAC MDM2 Degrader-8 (80 μM; 48 h) increases the proportion of cells in the G1 and G2 phases while decreasing the proportion of cells in the S phase in MDA-MB-231 cells, which manifests as G1-S and G2-M cell cycle arrest[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) increases p21 signaling in MDA-MB-231 cells in immunofluorescence assays[1].
MDM2 degradation induced by PROTAC MDM2 Degrader-8 (80 μM; 48 h) is reversed by MG-132 (30 μM; 2 h pre-exposure), while equivalent concentrations of GAA or VHL ligand alone fail to reduce MDM2 protein levels, supporting the necessity of intact PROTAC structure and the proteasome for MDM2 degradation[1].
PROTAC MDM2 Degrader-8 (3.13-100 μM; MDM2 protein 50 μg/mL; binding 400 s; dissociation 60 s) directly binds to MDM2 in SPR assays, with a KD of 38.2 μM[1].
PROTAC MDM2 Degrader-8 (30 min) enhances the thermal stability of MDM2 in CETSA, further supporting target engagement of MDM2 in cell-derived systems[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces MDM2 signaling in MDA-MB-231 cells in immunofluorescence assays[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) induces apoptosis in MDA-MB-231 cells, with the apoptosis rate reaching 48.39% at 80 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:V10: 80 μM; GAA: 80 μM; VHL ligand: 80 μM; MG-132: 30 μM
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Incubation Time:48 h; 2 h (MG-132 pre-treatment)
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Result:Decreased MDM2 protein levels.
GAA alone did not decrease MDM2 protein levels.
The VHL ligand alone did not decrease MDM2 protein levels.
MG-132 reversed MDM2 degradation.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:20, 40, 80 μM
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Incubation Time:48 h
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Result:Decreased MDM2 protein levels in a concentration-dependent manner.
Reached 51% MDM2 degradation at 80 μM.
Increased p21 protein levels.
Decreased the BCL-2/BAX ratio.
Decreased Cyclin B1 protein expression.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:20, 40, 80 μM
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Incubation Time:48 h
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Result:Increased apoptosis.
Produced an apoptotic rate of 48.39% at 80 μM.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:20, 40, 80 μM
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Incubation Time:24 h, 48 h
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Result:Inhibited migration by 55% at 24 h at 80 μM.
Inhibited migration by 69% at 48 h at 80 μM.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:20, 40, 80 μM
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Incubation Time:48 h
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Result:Increased the G1-phase population at 80 μM.
Decreased the S-phase population at 80 μM.
Increased the G2-phase population at 80 μM.
Produced G1-S and G2-M cell-cycle arrest.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:20, 40, 80 μM
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Incubation Time:48 h
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Result:Increased p21 mRNA expression.
In Vivo
PROTAC MDM2 Degrader-8 (12.5-50 μg/mL; aqueous solution exposure; 2 days) produces tumor growth inhibition rates of 16.8%, 23.4%, and 27.2%, respectively, in the MDA-MB-231 TNBC xenograft zebrafish model; the inhibition rate of the 15 μg/mL Cisplatin (HY-17394) positive control group is 33.2%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:3-dpf zebrafish[1]
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Dosage:6.25 μg/mL, 12.5 μg/mL, 25 μg/mL, 50 μg/mL, 100 μg/mL
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Administration:waterborne; continuous; 2 day exposure
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Result:Caused no mortality at 6.25, 12.5, 25, or 50 μg/mL.
Produced no apparent toxic phenotype at 6.25-50 μg/mL.
Caused 4 deaths among 30 zebrafish at 100 μg/mL.
Produced a mortality rate of 13% at 100 μg/mL.
Established an MTC of 50 μg/mL.
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Animal Model:2-dpf zebrafish; approximately 200 CM-DiI-labeled MDA-MB-231 cells microinjected into the yolk sac; model selected at 3 dpf[1]
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Dosage:12.5, 25, 50 μg/mL
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Administration:waterborne; continuous; 2 day exposure
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Result:Inhibited xenograft tumor growth by 16.8% at 12.5 μg/mL.
Inhibited xenograft tumor growth by 23.4% at 25 μg/mL.
Inhibited xenograft tumor growth by 27.2% at 50 μg/mL.
The 15 μg/mL cisplatin positive-control group produced 33.2% inhibition.
Chemical Information
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Molecular Weight 1315.70
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Formula C70H106N8O14S
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SMILES
O=C1C[C@@]2(C)[C@]([C@@H](O)C[C@@H]2[C@H](C)CC(C[C@@H](C)C(NCCOCCOCCOCCOCCN3CC(CCCCC(N[C@@H](C(C)(C)C)C(N4C[C@H](O)C[C@H]4C(N[C@@H](C)C5=CC=C(C6=C(C)N=CS6)C=C5)=O)=O)=O)N=N3)=O)=O)(C)C7=C1[C@]8(C)[C@](C[C@@H]7O)([H])C(C)(C)C(CC8)=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 MDM2 Degrader-8 Related Classifications
HY-162450 Related Classifications
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