PROTAC EGFR degrader 18
PROTAC EGFR degrader 18 is a VHL-based PROTAC degrader targeting EGFR. PROTAC EGFR degrader 18 inhibits tumor cell proliferation and induces apoptosis. When functionalized with hyaluronic acid, PROTAC EGFR degrader 18 achieves specific enrichment at tumor sites via CD44-mediated targeting, exerting anti-tumor activity while significantly reducing systemic toxicity. PROTAC EGFR degrader 18 can be used for the research of non-small cell lung cancer.
For research use only. We do not sell to patients.
- Formula: C57H75ClFN11O8S
- Molecular Weight:1128.79
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
VHL |
In Vitro
PRO NP + HA (1 nM-10 μM; 72 h) inhibits proliferation of HCC827 cells with an IC50 of 164 nM and PC-9 cells with an IC50 of 620 nM after 72 h of treatment, showing enhanced cytotoxicity compared to unmodified PRO NP[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCC827 cells
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Concentration:50-1000 nM (24 h incubation); 500 nM (time-course incubation)
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Incubation Time:24 h (concentration-dependent); 2-24 h (time-dependent)
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Result:Induced concentration-dependent EGFR degradation: at 300 nM, EGFR expression was significantly reduced, with maximal degradation at 500 and 1000 nM.
Exhibited time-dependent degradation, with increasing EGFR reduction from 2 to 24 h, and highest efficiency between 4-12 h.
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Cell Line:HCC827 cells
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Concentration:500-1000 nM PRO NP; 400 nM MG132; 10 μM gefitinib, 10 μM VHL ligand, 1 μM PRO NP
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Incubation Time:24 h (PRO NP/MG132 treatment); 4 h (preincubation), 24 h (PRO NP treatment)
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Result:MG132 significantly attenuated EGFR degradation induced by 500 nM and 1000 nM PRO NP.
Both gefitinib and VHL ligand markedly reduced PRO NP-mediated EGFR degradation.
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Cell Line:HCC827 cells, PC-9 cells
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Concentration:1 nM-10 μM
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Incubation Time:72 h
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Result:Inhibited proliferation of HCC827 cells with an IC50 of 314 nM.
Inhibited proliferation of PC-9 cells with an IC50 of 2.15 μM.\nInhibited proliferation of HCC827 cells with an IC50 of 164 nM, which was significantly lower than the IC50 of unmodified PRO NP.
Inhibited proliferation of PC-9 cells with an IC50 of 620 nM, which was significantly lower than the IC50 of unmodified PRO NP.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-inf | Vss | CL |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.v. | 6.65 h | 0.083 h | 40567 ng/mL | 11831 ng·h/mL | 0.417 L/kg | 14.5 mL/min/kg |
In Vivo
PRO NP + HA (15 mg/kg; i.v.; every other day; 8 doses) exhibits enhanced in vivo antitumor activity against HCC827 xenografts, achieving a tumor growth inhibition rate of 76.8% with favorable biosafety and improved tumor targeting[1].
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 mice (female, 18−20 g, subcutaneous xenograft of HCC827 cells)[1]
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Dosage:15 mg/kg
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Administration:i.v.; every other day; 8 doses
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Result:Achieved a tumor growth inhibition (TGI) rate of 66.4%.
Reduced Ki67 expression in tumor tissues.
Enhanced EGFR degradation in tumor tissues.
Increased apoptotic signals in tumors relative to the PRO group.
Caused no significant changes in mouse body weight.
Showed no pathological damage in major organs via H&E staining.
Resulted in liver (AST, ALT) and kidney (BUN, CRE) function indexes comparable to the control group.\nAchieved a tumor growth inhibition (TGI) rate of 76.8%.
Reduced Ki67 expression in tumor tissues.
Enhanced EGFR degradation in tumor tissues compared to both the free PRO control and unmodified PRO NP.
Induced the most intense apoptotic signals in tumors relative to the PRO and PRO NP groups.
Caused no significant changes in mouse body weight.
Showed no pathological damage in major organs via H&E staining.
Resulted in liver (AST, ALT) and kidney (BUN, CRE) function indexes comparable to the control group.
Accumulated at tumor sites in a time-dependent manner, reaching maximum retention at 24 hours post-injection, with significantly greater intratumoral accumulation than free Dir.
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Acute Systemic Toxicity Study
- Cell Viability Determination by MTT Colorimetric Assay
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Subchronic/Chronic Toxicity Study
- Apoptosis Solutions
- MTT Cell Proliferation Assay
Chemical Information
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Molecular Weight 1128.79
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Formula C57H75ClFN11O8S
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SMILES
FC(C(Cl)=C1)=CC=C1NC2=C3C(C=C(OC)C(OCCCN4CCN(C(CC[C@H](N)C(NCCCCCCC(N[C@H](C(C)(C)C)C(N5[C@@H](C(N[C@H](C)C6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@H](O)C5)=O)=O)=O)=O)CC4)=C3)=NC=N2
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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 EGFR degrader 18 Related Classifications
HY-184497 Related Classifications
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