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  3. Jun15702

Jun15702 is a PROTAC degrader targeting the capsid protein VP1 of enterovirus D68. Jun15702 recruits the Cereblon (CRBN) E3 ligase and activates the ubiquitin-proteasome pathway. Jun15702 inhibits viral entry and exerts inhibitory effects during the early, middle and late stages of viral replication. Jun15702 exhibits antiviral activity against multiple wild-type enterovirus D68 strains, and also shows submicromolar antiviral activity against the Pleconaril (HY-19952)-resistant enterovirus D68 variant rMO-VP1 F159V. Jun15702 can be used in studies related to enterovirus D68 (EV-D68) infection.
(Pink: Enterovirus ligand (HY-183010); Blue: Cereblon ligand (HY-183011); Black: linker).

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Jun15702

Jun15702 Chemical Structure

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Description

Jun15702 is a PROTAC degrader targeting the capsid protein VP1 of enterovirus D68. Jun15702 recruits the Cereblon (CRBN) E3 ligase and activates the ubiquitin-proteasome pathway. Jun15702 inhibits viral entry and exerts inhibitory effects during the early, middle and late stages of viral replication. Jun15702 exhibits antiviral activity against multiple wild-type enterovirus D68 strains, and also shows submicromolar antiviral activity against the Pleconaril (HY-19952)-resistant enterovirus D68 variant rMO-VP1 F159V. Jun15702 can be used in studies related to enterovirus D68 (EV-D68) infection[1]. (Pink: Enterovirus ligand (HY-183010); Blue: Cereblon ligand (HY-183011); Black: linker).

IC50 & Target

Cereblon

 

In Vitro

Jun15702 (10 μM; 0-8 h) depletes VP1 levels in EV-D68 US/MO/14-18947-infected RD cells when added before, during, or after viral entry, and effectively degrades the pleconaril-resistant VP1F159V mutant protein[1].
Jun15702 (0.3-30 μM; 2-10 h) induces dose-dependent, CRBN-mediated degradation of VP1 protein in EV-D68 US/MO/14-18947-infected RD cells, as confirmed by Western blot analysis[1].
Jun15702 (range; 60 h) has a CC50 of 81.8 μM in RD cells, showing no significant cytotoxicity at concentrations below 50 μM[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Immunofluorescence[1]

Cell Line: EV-D68 US/MO/14-18947-infected RD cells, rMO-VP1 F159V EV-D68-infected RD cells
Concentration: 10 μM
Incubation Time: -1-8 h, 0-8 h, 1-8 h, 2-8 h, 3-8 h, 4-8 h, 5-8 h, 6-8 h, 7-8 h (relative to infection; wild-type testing); 2-8 hpi (mutant strain testing)
Result: Nearly completely depleted VP1 levels when added before or during viral entry (-1-8 h, 0-8 h).
Retained potent inhibitory activity when added post-entry (2-8 h, 3-8 h, 4-8 h, 5-8 hpi), only gradually losing activity at 6-8 h and 7-8 hpi.
Dramatically reduced VP1 immunofluorescence signals when added at 2-8 hpi to rMO-VP1 F159V-infected cells, whereas pleconaril showed no inhibition.

Western Blot Analysis[1]

Cell Line: EV-D68 US/MO/14-18947-infected RD cells
Concentration: 0, 0.3, 1, 3, 10, 30 μM; 10 μM lenalidomide-5-Br combined with increasing concentrations of Jun15702
Incubation Time: 2-10 hpi
Result: Caused a dose-dependent reduction in VP1 protein levels, whereas pleconaril and lenalidomide-5-Br did not induce VP1 degradation.
Preserved VP1 degradation at concentrations above 3 μM when combined with 10 μM lenalidomide-5-Br.
Molecular Weight

949.97

Formula

C47H54F3N7O11

SMILES

O=C(NCCCOCCOCCOCCCNC(C1=NOC(CCCOC2=C(C=C(C=C2C)C3=NOC(C(F)(F)F)=N3)C)=C1)=O)CCCC#CC4=CC=C(CN(C5CCC(NC5=O)=O)C6=O)C6=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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References
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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Jun15702
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HY-182924
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