WCF-598
WCF-598 is a RXRγ (Kd: 234.2 nM) PROTAC degrader. WCF-598 induces RXRγ degradation via the ubiquitin-proteasome pathway and binds directly to RXRγ. WCF-598 indirectly induces AR-V7 degradation, impairs the stability of the RXRγ-AR-V7 complex, downregulates AR-V7 levels, and inhibits the transcription of downstream target genes of AR-V7. WCF-598 induces tumor cell apoptosis, inhibits cell proliferation, activates the p53 signaling pathway, and suppresses cell cycle progression. WCF-598 can be used for the research of prostate cancer.
(Pink: RXRγ ligand (HY-182352); Blue: Cereblon ligand (HY-138793); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3059574-58-9
- Formula: C54H63N5O7
- Molecular Weight:894.11
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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RXRγ |
Caspase 3 |
Caspase-7 |
WCF-598 (96 h) potently inhibits the viability of 22Rv1 cells with an IC50 of 13.56 nM, and exhibits an IC50 of 88.46 nM against VCaP-CRPC cells[1].
WCF-598 (6.25-6400 nM; 48 h) dose-dependently degrades RXRγ protein in 22Rv1 cells and VCaP-CRPC cells[1].
WCF-598 (6.25-6400 nM; 48 h) dose-dependently degrades AR-V7 protein in 22Rv1 cells, with a DC50 of 122.0 nM after 48 h of treatment[1].
WCF-598 (100-400 nM; 14 days) potently and concentration-dependently inhibits colony formation of 22Rv1 cells[1].
WCF-598 (100-400 nM; 72 h) induces apoptosis in 22Rv1 cells in a concentration-dependent manner, which is evidenced by increased levels of cleaved PARP and caspase-7, as well as enhanced Caspase-3/7 activity[1].
WCF-598 (100-400 nM; 48 h) activates p53-related pathways and inhibits cell cycle-related pathways in 22Rv1 cells in a concentration-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:22Rv1, VCaP-CRPC
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Concentration:6.25, 12.5, 25, 50, 100, 200, 400, 800, 1600, 3200, 6400 nM
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Incubation Time:48 h
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Result:Induced dose-dependent degradation of RXRγ in both cell lines, with DC50 values of 24.82 nM (22Rv1, maximal degradation 92.79%) and 27.15 nM (VCaP-CRPC, maximal degradation 82.01%).
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Cell Line:22Rv1
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Concentration:100, 200, 400 nM
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Incubation Time:72 h
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Result:Induced concentration-dependent apoptosis in 22Rv1 cells, demonstrated by increased levels of cleaved-PARP and caspase-7, and significantly elevated Caspase-3/7 activity at all tested concentrations.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | MRT0-t | F | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 3.0 mg/kg | i.v. | 3.85 h | 0.08 h | 39187.77 ng/mL | 17400.36 ng·h/mL | 0.86 h | / | 0.98 L/kg | 2.91 mL/min/kg |
| Rat[1] | 10.0 mg/kg | p.o. | 2.43 h | 0.83 h | 117.71 ng/mL | 243.45 ng·h/mL | 2.09 h | 0.42 % | / | / |
| Rat[1] | 5.0 mg/kg | i.p. | 7.69 h | 5.33 h | 743.64 ng/mL | 6649.49 ng·h/mL | 8.66 h | 22.93 % | / | / |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (male, 4 weeks old, injected subcutaneously with 22Rv1 CRPC cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; daily; 17 days
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Result:Achieved a tumor growth inhibition (TGI) value of 45.46% at 10 mg/kg.
Achieved a tumor growth inhibition (TGI) value of 61.18% at 20 mg/kg.
Significantly downregulated RXRγ protein levels in tumor tissues at both doses.
Induced degradation of androgen receptor (AR) and androgen receptor splice variant 7 (AR-V7) proteins in tumor tissues at both doses.
Caused no significant changes in mouse body weight during treatment.
Resulted in normal morphology and function of major organs (heart, liver, spleen, lung, kidney) per histopathological analysis.
Chemical Information
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CAS No. 3059574-58-9
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Molecular Weight 894.11
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Formula C54H63N5O7
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SMILES
O=C(CCCCCCCCCCCOC1=CC=CC2=C1CN(C2=O)C3CCC(NC3=O)=O)NC4=CC5=C(N(C6=CC7=C(C=C6C(C8=CC=C(C=C8)C(O)=O)=N5)C(C)(C)CCC7(C)C)C)C=C4
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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)
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