PROTAC PDE4 degrader-1
PROTAC PDE4 degrader-1 is an orally active CRBN-recruiting PDE4B PROTAC degrader. PROTAC PDE4 degrader-1 shows an IC50 of 1.9 μM against PDE4B, degrades PDE4B via the ubiquitin-proteasome pathway, and shows weak activity against PDE4C. PROTAC PDE4 degrader-1 inhibits the secretion of pro-inflammatory cytokines TNF-α and IL-6, reduces the infiltration of inflammatory cells into lung tissues, protects lung tissues and alleviates acute lung injury. PROTAC PDE4 degrader-1 can be used for the research of acute lung injury.
(Pink: PDE4 ligand (HY-174410); Blue: Cereblon ligand (HY-10984); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3087311-36-9
- Formula: C30H27F2N5O7S
- Molecular Weight:639.63
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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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Help & FAQs
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Biological Activity
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PDE4B 1.9 μM (IC50) |
PDE4B 41.98 μM (DC50) |
PDE4C |
IL-6 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| RAW264.7 | DC50 |
41.98 μM
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PDE4B protein degradation in mouse Raw264.7 cells assessed via Western blot after 1 hour pretreatment followed by 6 hours LPS incubation.
PDE4B protein degradation in mouse Raw264.7 cells assessed via Western blot after 1 hour pretreatment followed by 6 hours LPS incubation.
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40513451 |
| RAW264.7 | IC50 |
43.25 μM
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Inhibition of LPS-induced TNF-α secretion in mouse Raw264.7 cells measured by ELISA assay.
Inhibition of LPS-induced TNF-α secretion in mouse Raw264.7 cells measured by ELISA assay.
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40513451 |
| RAW264.7 | IC50 |
53.79 μM
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Inhibition of LPS-induced IL-6 secretion in mouse Raw264.7 cells measured by ELISA assay.
Inhibition of LPS-induced IL-6 secretion in mouse Raw264.7 cells measured by ELISA assay.
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40513451 |
PROTAC PDE4 degrader-1 (3087311-36-9) (compound 9 m) (10-80 μM) inhibits LPS-induced TNF-α and IL-6 secretion in Raw264.7 cells in a dose-dependent manner, with IC50 values of 43.25 μM and 53.79 μM, respectively[1].
PROTAC PDE4 degrader-1 inhibits the activity of purified PDE4B enzyme, with an IC50 of 1.9 μM, and exhibits at least 5-fold selectivity over other PDE family members[1].
PROTAC PDE4 degrader-1 (1.56-100 μM; 1 h pretreatment) selectively degrades PDE4B protein in Raw264.7 cells via the ubiquitin-proteasome pathway, with a DC50 of 41.98 μM, and exhibits extremely low activity against PDE4A, PDE4C and PDE4D[1].
PROTAC PDE4 degrader-1 (0.781-100 μM; 24 h) exhibits no cytotoxicity in Raw264.7, NIH-3 T3, MRC-5 or HepG2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Raw264.7 cells
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Concentration:30 μM (1 h pretreatment + 6 h LPS incubation); 1.56, 3.13, 6.25, 12.5, 25, 50, 75, 100 μM (1 h pretreatment + 6 h LPS incubation)
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Incubation Time:1 h (pretreatment); 6 h (LPS incubation)
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Result:Induced 80% degradation of PDE4B protein at 30 μM, showed weaker degradation of PDE4C, and had no effect on PDE4A or PDE4D protein levels.
Yielded a DC50 of 41.98 μM for PDE4B degradation in dose-dependent analysis.
Blocked degradation of PDE4B when co-treated with proteasome inhibitor MG132 (HY-13259).
Did not induce PDE4B degradation via individual components (warhead precursor 8c, PDE4 inhibitor 14h, cereblon ligand Pomalidomide (HY-10984)).
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Cell Line:Raw264.7, NIH-3 T3, MRC-5, HepG2 cells
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Concentration:1.56, 3.13, 6.25, 12.5, 25, 50, 75, 100 μM (Raw264.7, NIH-3 T3); 0.781, 1.562, 3.125, 6.25, 12.5, 25, 50, 100 μM (MRC-5, HepG2)
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Incubation Time:24 h
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Result:Exhibited no significant cytotoxicity in all four cell lines at concentrations up to 100 μM.
Maintained cell viability near 100% across all tested concentrations.
| Species | Dose | Route | Tmax | T1/2 | F | Cmax | AUC0-t | AUC0-∞ | C0 | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | p.o. | 0.25 h | 1.05 h | 20.99 % | 989 ng/mL | 1099 ng·h/mL | 1108 ng·h/mL | / | / | / |
| Mice | 5 mg/kg | i.v. | / | 0.59 h | / | / | 2618 ng·h/mL | 2622 ng·h/mL | 12450 ng/mL | 1823 mL/kg | 2026 mL/h/kg |
Chemical Information
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CAS No. 3087311-36-9
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Molecular Weight 639.63
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Formula C30H27F2N5O7S
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SMILES
O=C1CCC(C(N1)=O)N2C(C3=CC=CC(NCCNC(C4=CSC(C5=CC=C(C(OCC6CC6)=C5)OC(F)F)=N4)=O)=C3C2=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 PDE4 degrader-1 Related Classifications
HY-174405 Related Classifications
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