VVD 065
Based on 1 Customer Validation
VVD 065 is an orally active KEAP1-dependent NRF2 molecular glue degrader with a KEAP1 KD of 65 nM. VVD 065 covalently engages KEAP1 at Cys151, allosterically stabilizes KEAP1-CUL3 complex formation and enhances NRF2 polyubiquitination and proteasomal degradation. VVD 065 can be used for the research of esophageal squamous cell carcinoma, lung cancer, head-and-neck cancer, uterine cancers.
For research use only. We do not sell to patients.
- Purity : 99.71%
- CAS No.: 3034876-85-9
- Formula: C16H16ClN5O2
- Molecular Weight:345.78
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Storage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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
Biological Activity
Description
In Vitro
VVD 065 potently reduces NRF2 protein levels in wild-type KEAP1/NRF2, KEAP1-mutant, and NRF2-mutant cellular settings, inhibits NRF2-dependent gene expression, and suppresses proliferation of NRF2-dependent cancer cell lines at low nM concentrations[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
VVD-065 (2-50 mg/kg; p.o.; QD or BID) produces potent, sustained tumor growth inhibition in HCC95 xenograft mice[3].
VVD-065 (50 mg/kg; p.o.; QD or BID) drives tumor growth inhibition in diverse PDX models[3].
VVD-065 (50 mg/kg; p.o.; QD) improves overall survival and reduces tumor burden in orthotopic KLN-205 syngeneic mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG mice (inoculated 5 × 106 KYSE70 cells subcutaneously into the dorsal flank)[3]
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Dosage:5 mg/kg; 25 mg/kg; 50 mg/kg
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Administration:p.o.; QD or BID
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Result:Showed dose-dependent plasma exposure and intratumoral KEAP1_Cys151 target engagement.
Induced robust NRF2 protein degradation and reduced expression of NRF2 target genes (AKR1B10, AKR1C1, CYP4F11, NR0B1, SLC7A11) by >50% relative to vehicle at 5 mg/kg QD.
Achieved robust tumor growth inhibition (TGI) with significant suppression of tumor volume compared to vehicle control (P ≤ 0.0001) across all tested doses.
Achieved maximal KEAP1_Cys151 engagement shortly after single 5 mg/kg QD dosing, with engagement declining over 72 hours.
Maintained reduced NRF2 target gene and protein expression with repeat daily dosing for 7 days.
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Animal Model:NCG mice (inoculated 1 × 107 HCC95 cells subcutaneously into the dorsal flank)[3]
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Dosage:2 mg/kg; 10 mg/kg; 25 mg/kg; 50 mg/kg
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Administration:p.o.; QD or BID
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Result:Produced significant tumor growth inhibition compared to vehicle control (P ≤ 0.0001) across all tested doses.
Achieved durable suppression of tumor volume over 40 days of treatment.
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Animal Model:Immunodeficient mice[3]
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Dosage:50 mg/kg
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Administration:p.o.; QD or BID
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Result:Induced tumor growth inhibition (TGI) across wild-type and NRF2/KEAP1/CUL3 mutant PDX models, with the highest responses in NRF2 pathway-mutant tumors.
Produced significant tumor volume suppression compared to vehicle (P ≤ 0.0001) in LU1258 (CUL3S231L) sqNSCLC, LU6403 (CUL3R699T) sqNSCLC, LU6407 (NRF2R34P) sqNSCLC, LU6917 (KEAP1E218K) sqNSCLC, and HN0696 (NRF2R34P) HNSCC models.
Achieved durable partial regression for at least 90 days in the HN0696 model with continued treatment.
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Animal Model:DBA/2 mice (inoculated 2 × 105 KLN-205 cells subcutaneously into the dorsal flank)[3]
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Dosage:50 mg/kg
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Administration:p.o.; QD
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Result:Reduced lung tumor burden (evident via histologic analysis) in the orthotopic model.
Increased median overall survival from 30 days (vehicle) to 41 days (****, P < 0.0001) in the orthotopic model.
Significantly suppressed tumor volume compared to vehicle control (****, P ≤ 0.0001) in the heterotopic model.
Chemical Information
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CAS No. 3034876-85-9
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Appearance Solid
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Molecular Weight 345.78
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Formula C16H16ClN5O2
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Color White to off-white
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SMILES
C=CC(N1[C@H](C2=CC(C3=NC=NC(N)=N3)=CC(Cl)=C2)COCC1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (144.60 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 (stored under nitrogen). 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 (stored under nitrogen). 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: ≥ 1.25 mg/mL (3.62 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1.25 mg/mL (3.62 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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 (281 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 (stored under nitrogen). 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 | 2.8920 mL | 14.4601 mL | 28.9201 mL | 72.3003 mL |
| 5 mM | 0.5784 mL | 2.8920 mL | 5.7840 mL | 14.4601 mL | |
| 10 mM | 0.2892 mL | 1.4460 mL | 2.8920 mL | 7.2300 mL | |
| 15 mM | 0.1928 mL | 0.9640 mL | 1.9280 mL | 4.8200 mL | |
| 20 mM | 0.1446 mL | 0.7230 mL | 1.4460 mL | 3.6150 mL | |
| 25 mM | 0.1157 mL | 0.5784 mL | 1.1568 mL | 2.8920 mL | |
| 30 mM | 0.0964 mL | 0.4820 mL | 0.9640 mL | 2.4100 mL | |
| 40 mM | 0.0723 mL | 0.3615 mL | 0.7230 mL | 1.8075 mL | |
| 50 mM | 0.0578 mL | 0.2892 mL | 0.5784 mL | 1.4460 mL | |
| 60 mM | 0.0482 mL | 0.2410 mL | 0.4820 mL | 1.2050 mL | |
| 80 mM | 0.0362 mL | 0.1808 mL | 0.3615 mL | 0.9038 mL | |
| 100 mM | 0.0289 mL | 0.1446 mL | 0.2892 mL | 0.7230 mL |
VVD 065 Related Classifications
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