WWQ-03-012
Based on 1 Customer Validation
WWQ-03-012 is a selective DESI2 inhibitor with an IC50 of 47.3 nM. WWQ-03-012 binds covalently to DESI2, blocks its enzymatic activity, and inhibits DESI2-mediated deSUMOylation, deubiquitination and stabilization of mutant JAK2, thereby promoting the complete degradation of mutant JAK2 via the intracellular ubiquitin-proteasome system and inducing apoptosis, while exerting no significant effect on wild-type JAK2. WWQ-03-012 can be used for research on myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML), especially for hematological malignancies carrying the JAK2-V617F mutation and those resistant to Ruxolitinib (HY-50856).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 98.04%
- CAS. Nr.: 3076807-15-0
- Formel: C20H16N4O3S
- Molecular Weight:392.43
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Speicherung: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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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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JAK2 |
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Cell Line
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Type | Value | Description | References |
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| HEL | DC50 |
543.6 nM
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Dose-dependent degradation of JAK2-V617F in human HEL (JAK2-V617F) cells assessed via western blot analysis after 24 h incubation.
Dose-dependent degradation of JAK2-V617F in human HEL (JAK2-V617F) cells assessed via western blot analysis after 24 h incubation.
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41332324 |
WWQ-03-012 (with 6 h pre-incubation and 30 min substrate reaction) potently and selectively inhibits the enzymatic activity of recombinant DESI2, with an IC50 value of 47.3 nM[1].
WWQ-03-012 (100 μM) enhances the thermal stability of the target protein in recombinant experiments with purified DESI2 protein, causing a thermal shift of up to 3.5 °C[1].
WWQ-03-012 (24-48 h) exhibits highly selective cytotoxicity in wild-type (WT) or JAK2-V617F-mutant MPN/AML cell lines, normal mouse CD34+ cells, bone marrow from healthy donors, and primary MPN samples (mutCALR or JAK2-V617F). It significantly and preferentially kills cells carrying the JAK2-V617F mutation, while exerting minimal effects on wild-type and CALR-mutant cells[1].
WWQ-03-012 (0.1-10 μM; 24 h) exerts a selective degradation effect on mutant proteins in multiple JAK2-WT (K562) and JAK2-V617F mutant (HEL (DC50 = 543.6 nM), DAMI, UKE-1, Ba/F3-JAK2-V617F) cell lines. It significantly induces JAK2-V617F degradation in a concentration-dependent manner, but has no obvious effect on the protein level of wild-type JAK2 (WT)[1].
WWQ-03-012 (1 μM-10 μM; 24 h) promotes ubiquitination and SUMOylation of the mutant protein in HEL cells (JAK2-V617F), leading to a robust increase in polyubiquitin and SUMO2/3/4 signals on immunoprecipitated JAK2-V617F, accompanied by its protein degradation[1].
WWQ-03-012 (10 μM; 24 h) also exhibits high targeting selectivity in mutant-driven MPN samples and UT7-MPLW515L cells, specifically degrading the JAK2-V617F protein without inducing degradation of JAK2 (WT) in mutCALR- or MPL-mutated samples[1].
Combination treatment with WWQ-03-012 (24 h) and Ruxolitinib (HY-50856) exerts synergistic cytotoxic effects on Ba/F3-JAK2-V617F cells and samples from drug-resistant patients, and significantly reduces the relative viability of cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Multiple mutated or wild-type cell models (PBMCs, HEL, CD34+ cells, Ba/F3, healthy bone marrow samples)
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Concentration:0.1, 0.3, 1.0, 1.25, 2.5, 3.0, 5.0, 10.0, 20.0 μM
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Incubation Time:24, 48 h
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Result:Demonstrated significantly stronger cytotoxicity (smaller GI50 values) against cell lines harboring the mutation in a comparison between wild-type and JAK2-V617F-mutated MPN/AML cell lines.
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Cell Line:K562 (JAK2-WT) and multiple JAK2-V617F cell lines (HEL, DAMI, UKE-1, Ba/F3-JAK2-V617F)
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Concentration:1, 3, 10 μM
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Incubation Time:24 h
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Result:Thoroughly depleted the expression level of the mutant JAK2 protein in a dose-dependent manner across all JAK2-V617F-positive leukemia cell lines.
Left the protein level of wild-type JAK2 in K562 cells completely stable under identical treatment concentrations, proving its degradation mechanism possesses extremely high mutation selectivity.
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Cell Line:Induced Ruxolitinib-persistent/resistant cell lines (MPN-RR, Ruxolitinib-RR)
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Concentration:0.625, 1.25, 2.5, 5.0, 10.0 μM
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Incubation Time:24 h, 72 h
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Result:Effectively overcame the drug resistance induced by targeted kinase inhibitors, substantially suppressing the proliferation of Ruxolitinib-resistant clonal populations.
Demonstrated an anti-survival effect significantly superior to continuous exposure to the original drug (Ruxolitinib).
WWQ-03-012 (12.5 mg/kg; i.p.; twice daily; 15 days) significantly reduces JAK2V617F-driven MPN pathology in transgenic mice, including correcting peripheral blood abnormalities, reducing erythroid hyperplasia and splenomegaly, and suppressing leukemic stem cell populations, with minimal toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD scid gamma (NSG) (female, 6-8 weeks old, acute myeloid leukemia xenograft model via tail vein injection of HEL-Luc+GFP+ JAK2-V617F cells)[1]
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Dosage:12.5 mg/kg
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Administration:i.p.; twice daily; up to 24 days
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Result:Achieved significantly slower tumor growth and reduced leukemia burden compared to vehicle control, with potency comparable to a comparator reagent.
Reduced human JAK2-V617F levels (GFP+JAK2+) in bone marrow by ≈ 4-fold compared to the vehicle group.
Showed no significant difference in body weight compared to other groups.
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Animal Model:JAK2-V617F transgenic (C57BL/6XDBA/2 F2 background, 8 weeks old, myeloproliferative neoplasm model via vav gene promoter-driven JAK2-V617F expression)[1]
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Dosage:12.5 mg/kg
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Administration:i.p.; twice daily; 15 days
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Result:Significantly reduced RBC, HGB, and HCT counts, as well as immature reticulocyte levels in peripheral blood.
Reduced erythroid hyperplasia in the bone marrow, ameliorated splenomegaly, and diminished LSC populations.
Confirmed reduced JAK2-V617F protein levels and downstream signaling in bone marrow cells via western blot analysis.
Showed no significant body weight differences compared to control groups.
Chemical Information
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CAS. Nr. 3076807-15-0
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Appearance Solid
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Molecular Weight 392.43
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Formel C20H16N4O3S
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Color White to off-white
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SMILES
O=C([C@@H]1CN(C#N)CC1)NC(S2)=NC3=C2C=CC(C4=CC(OCO5)=C5C=C4)=C3
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
DMSO : 100 mg/mL (254.82 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.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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 (6.37 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 (6.37 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.
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.
Reinheit & Dokumentation
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Data Sheet (282 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
Verweise
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 |
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| DMSO | 1 mM | 2.5482 mL | 12.7411 mL | 25.4823 mL | 63.7056 mL |
| 5 mM | 0.5096 mL | 2.5482 mL | 5.0965 mL | 12.7411 mL | |
| 10 mM | 0.2548 mL | 1.2741 mL | 2.5482 mL | 6.3706 mL | |
| 15 mM | 0.1699 mL | 0.8494 mL | 1.6988 mL | 4.2470 mL | |
| 20 mM | 0.1274 mL | 0.6371 mL | 1.2741 mL | 3.1853 mL | |
| 25 mM | 0.1019 mL | 0.5096 mL | 1.0193 mL | 2.5482 mL | |
| 30 mM | 0.0849 mL | 0.4247 mL | 0.8494 mL | 2.1235 mL | |
| 40 mM | 0.0637 mL | 0.3185 mL | 0.6371 mL | 1.5926 mL | |
| 50 mM | 0.0510 mL | 0.2548 mL | 0.5096 mL | 1.2741 mL | |
| 60 mM | 0.0425 mL | 0.2124 mL | 0.4247 mL | 1.0618 mL | |
| 80 mM | 0.0319 mL | 0.1593 mL | 0.3185 mL | 0.7963 mL | |
| 100 mM | 0.0255 mL | 0.1274 mL | 0.2548 mL | 0.6371 mL |
WWQ-03-012 Related Classifications
HY-180561 Related Classifications
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