WWZ-11-098
Based on 1 Customer Validation
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.
- Purity: 98.27%
- Formula: C39H47F3N8O7S
- Molecular Weight:828.90
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
CDK6 2.6 nM (DC50) |
In Vitro
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.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | Tmax | AUC0-∞ | AUC0-t | F | C0 | CL |
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| 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 % | / | / |
In Vivo
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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Appearance Solid
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Molecular Weight 828.90
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Formula C39H47F3N8O7S
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Color White to off-white
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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
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (120.64 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (6.03 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (275 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.2064 mL | 6.0321 mL | 12.0642 mL | 30.1605 mL |
| 5 mM | 0.2413 mL | 1.2064 mL | 2.4128 mL | 6.0321 mL | |
| 10 mM | 0.1206 mL | 0.6032 mL | 1.2064 mL | 3.0160 mL | |
| 15 mM | 0.0804 mL | 0.4021 mL | 0.8043 mL | 2.0107 mL | |
| 20 mM | 0.0603 mL | 0.3016 mL | 0.6032 mL | 1.5080 mL | |
| 25 mM | 0.0483 mL | 0.2413 mL | 0.4826 mL | 1.2064 mL | |
| 30 mM | 0.0402 mL | 0.2011 mL | 0.4021 mL | 1.0053 mL | |
| 40 mM | 0.0302 mL | 0.1508 mL | 0.3016 mL | 0.7540 mL | |
| 50 mM | 0.0241 mL | 0.1206 mL | 0.2413 mL | 0.6032 mL | |
| 60 mM | 0.0201 mL | 0.1005 mL | 0.2011 mL | 0.5027 mL | |
| 80 mM | 0.0151 mL | 0.0754 mL | 0.1508 mL | 0.3770 mL | |
| 100 mM | 0.0121 mL | 0.0603 mL | 0.1206 mL | 0.3016 mL |
WWZ-11-098 Related Classifications
HY-181490 Related Classifications
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