PROTAC 3CPro degrader-1
PROTAC 3CPro degrader-1 is a picornavirus 3C protease (3CPro) PROTAC degrader with an DC50 value of 0.16 μM. PROTAC 3CPro degrader-1 directly inhibits the catalytic function of 3CPro, induces degradation via the ubiquitin-proteasome pathway, and binds to CRBN to form a ternary complex. PROTAC 3CPro degrader-1 inhibits viral replication, degrades drug-resistant EV71 3CPro mutants, and exhibits broad-spectrum activity against multiple picornavirus 3CPro variants. PROTAC 3CPro degrader-1 can be used in studies related to picornavirus infections.
(Pink: Virus Protease Target protein ligand; Blue: Cereblon ligand (HY-23095); Black: linker).
For research use only. We do not sell to patients.
- Formula: C42H51FN6O10
- Molecular Weight:818.89
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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
- Purity & Documentation
- References
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Biological Activity
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | DC50 |
0.16 μM
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Degradation of wild-type EV71 3CPro-Flag in HEK293T cells stably expressing the protein, assessed by Western blotting after 24 h incubation.
Degradation of wild-type EV71 3CPro-Flag in HEK293T cells stably expressing the protein, assessed by Western blotting after 24 h incubation.
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PMC13379210 |
| RD | EC50 |
1.17 μM
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Inhibition of EV71 replication in infected RD cells, assessed by qPCR quantification of viral mRNA after 24 h incubation.
Inhibition of EV71 replication in infected RD cells, assessed by qPCR quantification of viral mRNA after 24 h incubation.
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PMC13379210 |
| RD | EC50 |
0.83 μM
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Inhibition of HRV replication in infected RD cells.
Inhibition of HRV replication in infected RD cells.
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PMC13379210 |
| RD | EC50 |
0.93 μM
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Inhibition of CVA16 replication in infected RD cells.
Inhibition of CVA16 replication in infected RD cells.
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PMC13379210 |
| RD | EC50 |
0.04 μM
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Inhibition of CVA10 replication in infected RD cells.
Inhibition of CVA10 replication in infected RD cells.
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PMC13379210 |
| RD | EC50 |
0.76 μM
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Inhibition of CVA6 replication in infected RD cells.
Inhibition of CVA6 replication in infected RD cells.
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PMC13379210 |
| RD | EC50 |
0.28 μM
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Inhibition of CVB5 replication in infected RD cells.
Inhibition of CVB5 replication in infected RD cells.
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PMC13379210 |
| RD | EC50 |
2.35 μM
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Inhibition of ECHO11 replication in infected RD cells.
Inhibition of ECHO11 replication in infected RD cells.
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PMC13379210 |
PROTAC 3CPro degrader-1 (compound D34) potently inhibits the catalytic activity of purified EV71 3CPro, with an IC50 of 0.57 μM[1].
PROTAC 3CPro degrader-1 (0.08-20 μM; 24 h) induces rapid, sustained, and concentration-dependent degradation of wild-type EV71 3CPro in HEK293T cells stably expressing EV71 3CPro-Flag, with a DC50 of 0.16 μM[1].
PROTAC 3CPro degrader-1 (2 μM; 24 h) mediates the degradation of EV71 3CPro in HEK293T cells stably expressing EV71 3CPro-Flag in a manner strictly dependent on covalent bond formation with Cys147 and activation of the ubiquitin-proteasome system, and requires simultaneous binding to both EV71 3CPro and CRBN[1].
PROTAC 3CPro degrader-1 (0.08-20 μM; 24 h) effectively degrades various EV71 3CPro drug-resistant mutants (N69S, S41M, S41I, L102A, T106E) in stably transfected HEK293T cells, indicating that it has a high viral resistance barrier[1].
PROTAC 3CPro degrader-1 potently inhibits EV71 replication in infected RD cells, with an EC50 of 1.17 μM. Its mechanism of action involves dual pathways: direct inhibition of EV71 3CPro and CRBN-dependent protein degradation[1].
PROTAC 3CPro degrader-1 (0.08-20 μM; 24 h) exhibits broad-spectrum degradation activity against 3CPro derived from various picornaviruses (CVA16, CVB3, HRV, PV, ECHO) in stably transfected HEK293T cells[1].
PROTAC 3CPro degrader-1 exhibits broad-spectrum antiviral activity against multiple picornaviruses in infected RD cells, with EC50 values ranging from 0.04 μM to 2.35 μM[1].
PROTAC 3CPro degrader-1 (3.125-100 μM; 24 h) shows no obvious cytotoxicity against HEK293T and RD cells even at the highest concentration of 100 μM after 24 h of treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T cells stably expressing wild-type EV71 3CPro-Flag
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Concentration:0.08, 0.16, 0.3, 0.6, 1.2, 2.5, 5, 10, 20 μM (concentration-dependent testing)
2 μM (time-course testing) -
Incubation Time:24 h (concentration-dependent testing)
3, 6, 12, 24, 48 h (time-course testing) -
Result:Induced concentration-dependent degradation of EV71 3CPro, with a DC50 of 0.16 μM.
Achieved significant degradation after 12 h of incubation with 2 μM.
Achieved near-complete degradation by 24 h of incubation with 2 μM.
Maintained stable degradation activity at 36 and 48 h of incubation with 2 μM.
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Cell Line:HEK293T cells stably expressing wild-type EV71 3CPro-Flag or EV71 3CPro(C147A)-Flag
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Concentration:2 μM (covalent dependency testing), 10 μM A8, 10 μM Pomalidomide (HY-10984), 5 μM MLN4924 (HY-70062), 5 μM TAK-243 (HY-100487), 5 μM Carfilzomib (HY-10455), 5 μM bortezomib (HY-10227) (pre-incubation)
5, 10 μM plus 5 μM MG132 (HY-13259) (ubiquitination testing) -
Incubation Time:24 h (covalent dependency testing); 4 h (pre-incubation)
12 h (ubiquitination testing) -
Result:Failed to degrade EV71 3CPro(C147A)-Flag or induce degradation in cells treated with non-covalent derivative D34-1.
Blocked EV71 3CPro degradation when cells were pre-treated with A8, pomalidomide, MLN4924, TAK-243, carfilzomib, or bortezomib.
Increased ubiquitination levels of EV71 3CPro.
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Cell Line:HEK293T cells stably expressing EV71 3CPro mutants (N69S, S41M, S41I, L102A, T106E)
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Concentration:0.08, 0.16, 0.3, 0.6, 1.2, 2.5, 5, 10, 20 μM (N69S testing)
1, 3, 10 μM (S41M, S41I, L102A, T106E testing) -
Incubation Time:24 h
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Result:Exhibited varying degrees of degradation activity against all tested EV71 3CPro mutants.
Showed the most potent degradation activity for the N69S mutant.
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Cell Line:HEK293T cells, RD cells
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Concentration:3.125, 6.25, 12.5, 25, 50, 100 μM
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Incubation Time:24 h
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Result:Caused no significant reduction in cell number at concentrations up to 100 μM in HEK293T cells.
Caused no significant reduction in cell number at concentrations up to 100 μM in RD cells.
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Cell Line:HEK293T cells stably expressing picornaviral 3CPro (CVA16, CVB3, HRV, PV, ECHO)
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Concentration:0.08, 0.16, 0.3, 0.6, 1.2, 2.5, 5, 10, 20 μM
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Incubation Time:24 h
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Result:Induced significant degradation of 3CPro across all tested picornavirus species.
Showed the most pronounced degradation activity for EV71 3CPro.
| Species | Dose | Route | Cmax | T1/2 | Tmax | CL | Vss | MRT | AUC0-t |
|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 2 mg/kg | i.v. | 407 ng/mL | 3.17 h | 0.25 h | 84.22 mL/min/kg | 4.48 L/kg | 0.88 h | 392.67 ng·h/mL |
Chemical Information
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Molecular Weight 818.89
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Formula C42H51FN6O10
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SMILES
FC1=CC=C(C[C@@H](C(N[C@@H](C[C@@H]2CCCNC2=O)C=O)=O)NC([C@H](C(C)C)NC(CCCCCCOC3=CC=C(C(N(C4C(NC(CC4)=O)=O)C5=O)=O)C5=C3)=O)=O)C=C1
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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 3CPro degrader-1 Related Classifications
HY-187716 Related Classifications
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