WIZ degrader 9
Based on 1 Customer Validation
WIZ degrader 9 is an orally active molecular glue degrader of the WIZ transcription factor. As a molecular glue, WIZ degrader 9 recruits WIZ to the cereblon E3 ubiquitin ligase complex via its ZF7 domain, driving proteasome-dependent degradation of WIZ. WIZ degrader 9 induces hemoglobin production, reduces the level of H3K9 dimethylation across the whole genome and at the β-globin locus, upregulates the transcription of γ-globin and BGLT3, and increases the level of histone H3K9 acetylation in the promoter region of HBG1/2. WIZ degrader 9 effectively induces fetal hemoglobin production in both mice and cynomolgus monkeys. WIZ degrader 9 can be used for research on sickle cell disease.
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- Purity: 99.29%
- CAS No.: 2654011-51-3
- 화학식: C21H27N3O4
- 분자량:385.46
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보관:
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, 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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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Epigenetics Compound Library
HY-L005
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Histone Modification Research Compound Library
HY-L024
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Anti-Cardiovascular Disease Compound Library
HY-L046
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Orally Active Compound Library
HY-L061
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Molecular Glue Compound Library
HY-L137
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Anti-Hematopathy Compound Library
HY-L171
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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High-Throughput Bioactive Compound Library
HY-L205
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Molecular Glue-like Compound Library
HY-L918
Biological Activity
WIZ degrader 9 (dWIZ-2) (10 μM; 7 days) induces dose-dependent HbF in primary human erythroblasts from healthy donors without affecting erythroid differentiation or proliferation; treatment at 10 μM for 7 days reduces the global H3K9me2 level by 15.4%[1].
WIZ degrader 9 (1-10 μM; applied until day 18 of differentiation) induces dose-dependent degradation of WIZ and promotes HbF expression in primary human erythroid progenitor cells from patients with sickle cell disease (SCD); it increases total HbF to 35.5% at 1 μM and to 45% at 10 μM, while maintaining normal erythroid differentiation and maturation[1].
WIZ degrader 9 (days 1-7 of differentiation) reduces WIZ binding genome-wide and within the β-globin locus, decreases the repressive H3K9me2 modification, increases the active H3K9ac level at the fetal globin gene promoter, and upregulates the expression of genes including the fetal globin-associated gene BGLT3 in primary human erythroblasts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | F | Tmax | T1/2 |
|---|---|---|---|---|---|
| Cynomolgus Monkey[1] | 30 mg/kg | p.o. | 72 % | 1 to 2 h | 12 to 16 min |
WIZ degrader 9 (30 mg/kg; p.o.; once daily; for 28 consecutive days) induces sustained degradation of WIZ and significant expression of fetal hemoglobin in healthy cynomolgus monkeys. In responding animals, the proportion of HbF+ reticulocytes reaches up to 90%, and the proportion of HbF+ erythrocytes reaches 20%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NBSGW mice (immunocompromised, humanized with healthy human donor CD34+ hematopoietic stem and progenitor cells)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Induced dose-dependent WIZ degradation in bone marrow CD71+ human erythroblasts, with mean 65% degradation at the highest dose.
Increased the proportion of HbF+ human erythroblasts up to 42% at the highest dose, compared to vehicle control levels.
Reached HbF levels up to 19% at the highest dose, compared to <0.8% in vehicle controls.
Increased γ-globin mRNA transcript levels up to 26% of total β-like globin transcript, compared to 2% in vehicle controls.
Showed positive correlation between increase in HbF+ cells and fractional HbF expression measured by HPLC.
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Animal Model:healthy, naïve[1]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Induced rapid (within 6 hours), deep (>75%), and durable (>24 hours) WIZ degradation in peripheral blood CD3+ cells after the first dose.
Increased γ-globin mRNA levels to a median of 25% of total γ- and β-globin transcript (range 3 to 37% in responding animals) by day 28.
Increased HbF+ peripheral blood CD71+ reticulocytes to >90% in two of three responding animals by day 28.
Increased HbF+ red blood cells up to 20% in responding animals.
Was well-tolerated, with no significant changes to peripheral blood platelet counts, hematocrit, or neutrophil counts compared to pre-dose levels.
Chemical Information
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CAS No. 2654011-51-3
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Appearance Solid
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분자량 385.46
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화학식 C21H27N3O4
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Color White to off-white
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SMILES
O=C(C(N(CC1=C2C=CC(OC[C@@H]3N(CC)CCCC3)=C1)C2=O)CC4)NC4=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
용액&용해도
DMSO : 100 mg/mL (259.43 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 (protect from light, 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 (protect from light, 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)
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: ≥ 2.5 mg/mL (6.49 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.49 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
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 (protect from light, 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.
순도&문서
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Data Sheet (277 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 (protect from light, 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 | 2.5943 mL | 12.9715 mL | 25.9430 mL | 64.8576 mL |
| 5 mM | 0.5189 mL | 2.5943 mL | 5.1886 mL | 12.9715 mL | |
| 10 mM | 0.2594 mL | 1.2972 mL | 2.5943 mL | 6.4858 mL | |
| 15 mM | 0.1730 mL | 0.8648 mL | 1.7295 mL | 4.3238 mL | |
| 20 mM | 0.1297 mL | 0.6486 mL | 1.2972 mL | 3.2429 mL | |
| 25 mM | 0.1038 mL | 0.5189 mL | 1.0377 mL | 2.5943 mL | |
| 30 mM | 0.0865 mL | 0.4324 mL | 0.8648 mL | 2.1619 mL | |
| 40 mM | 0.0649 mL | 0.3243 mL | 0.6486 mL | 1.6214 mL | |
| 50 mM | 0.0519 mL | 0.2594 mL | 0.5189 mL | 1.2972 mL | |
| 60 mM | 0.0432 mL | 0.2162 mL | 0.4324 mL | 1.0810 mL | |
| 80 mM | 0.0324 mL | 0.1621 mL | 0.3243 mL | 0.8107 mL | |
| 100 mM | 0.0259 mL | 0.1297 mL | 0.2594 mL | 0.6486 mL |
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