WWZ-11-098
WWZ-11-098 is a selective CDK6 PROTAC degrader with DC50 of 2.6 nM. WWZ-11-098 induces degradation of CDK6 in a CRBN-dependent manner, while sparing CDK1, CDK2, CDK4, and CDK9. WWZ-11-098 induces apoptosis, G1-S cell cycle arrest and shows anti-proliferative activity in cancer cells. WWZ-11-098 exhibits antitumor efficacy in a xenograft model without signs of toxicity. WWZ-11-098 can be used for the research of leukemia.
(Pink: CDK6 ligand (HY-181501); Blue: Cereblon E3 ligase ligand; Black: linker).
For research use only. We do not sell to patients.
- Formula: C39H47F3N8O7S
- Molecular Weight:828.90
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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
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Biological Activity
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CDK6 2.6 nM (DC50) |
WWZ-11-098 ( 5 days) potently inhibits the proliferation of MOLT-4 cells (IC50 = 70 nM) and MV4-11 cells (IC50 = 0.13 μM)[1].
WWZ-11-098 (10 nM-10 μM; 3-24 h) potently and selectively degrades CDK6 in MOLT-4 cells with a DC50 of 2.6 nM, achieving over 98% degradation at 100 nM for 24 h, while sparing CDK1, CDK2, CDK4, and CDK9, via a CRBN-dependent mechanism[1].
WWZ-11-098 (100-200 nM; 48 h) induces G1-S cell cycle arrest and induces apoptosis in MOLT-4 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MOLT-4 cells
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Concentration:10, 100 nM, 10 μM
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Incubation Time:3, 6, 9, 12, 24 h
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Result:Achieved 98% degradation of CDK6 at 100 nM for 24 h.
Induced dose-dependent CDK6 degradation with a DC50 of 2.6 nM and a Dmax exceeding 99%, with no hook effect up to 10 μM.
Depleted over 80% of CDK6 within 3 h of treatment with 100 nM.
Showed rescued CDK6 degradation by pre-treatment with CDK2/4/6 inhibitor, MG132 (HY-13259), confirming CRBN-dependent activity via the ubiquitin-proteasome pathway.
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Cell Line:MOLT-4 cells
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Concentration:100, 200 nM
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Incubation Time:48 h
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Result:Induced G1-S cell cycle arrest in MOLT-4 cells, with a stronger effect than control compounds at equivalent concentrations.
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Cell Line:MOLT-4 cells
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Concentration:100, 200 nM
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Incubation Time:48 h
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Result:Significantly promoted apoptosis in MOLT-4 cells, with superior efficacy compared to control compounds.
| Species | Dose | Route | T1/2 | Cmax | Tmax | AUC0-∞ | AUC0-t | F | C0 | CL |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.v. | 2.64 ± 0.899 h | 11833 ± 1242 ng/mL | 0.0833 ± 0.000 h | 7821 ± 1464 ng·h/mL | 7766 ± 1393 ng·h/mL | / | 17358 ± 2227 ng/mL | 655 ± 123 mL/h/kg |
| Mice[1] | 20 mg/kg | p.o. | 0.293 ± 0.0441 h | 294 ± 155 ng/mL | 0.250 ± 0.00 h | 203 ± 97.4 ng·h/mL | 201 ± 97.5 ng·h/mL | 0.647 ± 0.31 % | / | / |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (male, 4-6 weeks old, 18-22 g, MOLT-4 cell line xenograft model)[1]
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Dosage:10 mg/kg
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Administration:21 days
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Result:Induced sustained degradation of CDK6 and corresponding reductions of phosphorylated retinoblastoma protein (p-RB) in tumor tissues 6 hours after final dose at day 3.
Significantly suppressed MOLT-4 xenograft tumor growth, with marked reductions in both tumor volume and final tumor weight.
Caused no significant body weight loss throughout the study.
Chemical Information
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Molecular Weight 828.90
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Formula C39H47F3N8O7S
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SMILES
COC1=C(C=C(C=C1)C(N2[C@H](CN(C[C@@H]2C)C3=CC=C(C=C3)S(=O)(N4CCC(CC4)NC5=NC=C(C(OC6CCCC6)=N5)C(F)(F)F)=O)C)=O)N7CCC(NC7=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)
WWZ-11-098 Related Classifications
HY-181490 Related Classifications
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