GMB-475
Based on 1 Customer Validation
GMB-475 is a potent BCR-ABL1 PROTAC based on Von Hippel-Lindau (VHL). GMB-475 targets the nutmeg pocket of ABL1 in an ectopic manner and degrades BCR-ABL1 protein through the ubiquitin proteasome pathway. GMB-475 inhibits the proliferation of human K562 cells and mouse Ba/F3 cells, and is used for the study of chronic myeloid leukemia.
(Pink: BCR-ABL1 ligand (HY-11007); Blue: VHL ligand (HY-125845); Black: linker).
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- Pureza: 98.69%
- No. CAS: 2490599-18-1
- Fòrmula: C43H46F3N7O7S
- Peso molecular:861.93
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
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Actividad biológica
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STAT5 |
VHL |
Bcr-Abl |
GMB-475 (0.01-100 μM, 3 days) inhibits leukemic stem cell viability in chronic myeloid leukemia (CML) by targeting degradation of BCR-ABL1 protein kinase and inhibiting downstream STAT5 biomarkers[1]. GMB-475 (0-5 μM, 48 h) blocks multiple molecules in the JAK-STAT pathway, blocks the cell cycle and promotes apoptosis in Ba/F3 cells harboring the BCR::ABL1 mutant[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human K562 cells and murine BCR-ABL1 transformed Ba/F3 cells
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Concentration:0.01-100 μM
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Incubation Time:3 days
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Result:Inhibited the proliferation of two types of cells, with an IC50 value of approximately 1 μM.
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Cell Line:Ba/F3-MIG-p210 cells carrying BCR::ABL1T315I+F486S mutations
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Concentration:0-5 μM
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Incubation Time:48 h
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Result:Exhibited a growth inhibition effect on Ba/F3-MIG-p210 cells carrying BCR::ABL1T315I+F486S mutations, with an IC50 value of 4.49 µM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:8-week-old Balb/c mice were injected with Ba/F3-MG-p210-Luc cells via tail vein to establish a chronic myeloid leukemia (CML) mouse model[2].
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Dosage:5 mg/kg
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Administration:Intraperitoneal injection (i.p.); once every two days; 10 days
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Result:Showed a trend of reducing the tumor burden and prolonging the survival of the CML mouse model.
Chemical Information
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No. CAS 2490599-18-1
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Appearance Solid
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Peso molecular 861.93
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Fòrmula C43H46F3N7O7S
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Color Light yellow to yellow
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SMILES
FC(F)(F)OC1=CC=C(NC2=CC(C3=CC=C(OCCOCC(N[C@@H](C(C)(C)C)C(N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)C[C@@H](O)C4)=O)=O)C=C3)=NC=N2)C=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvente y solubilidad
DMSO : 250 mg/mL (290.05 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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: ≥ 6.25 mg/mL (7.25 mM); Clear solution
This protocol yields a clear solution of ≥ 6.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (62.5 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.
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.
Pureza y Documentación
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Ficha de datos (273 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Burslem GM, et al. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. [Content Brief]
[2]. Ye W, et al. The proteolysis targeting chimera GMB-475 combined with dasatinib for the treatment of chronic myeloid leukemia with BCR::ABL1 mutants. Front Pharmacol. 2022 Oct 3;13:931772. [Content Brief]
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1602 mL | 5.8009 mL | 11.6019 mL | 29.0047 mL |
| 5 mM | 0.2320 mL | 1.1602 mL | 2.3204 mL | 5.8009 mL | |
| 10 mM | 0.1160 mL | 0.5801 mL | 1.1602 mL | 2.9005 mL | |
| 15 mM | 0.0773 mL | 0.3867 mL | 0.7735 mL | 1.9336 mL | |
| 20 mM | 0.0580 mL | 0.2900 mL | 0.5801 mL | 1.4502 mL | |
| 25 mM | 0.0464 mL | 0.2320 mL | 0.4641 mL | 1.1602 mL | |
| 30 mM | 0.0387 mL | 0.1934 mL | 0.3867 mL | 0.9668 mL | |
| 40 mM | 0.0290 mL | 0.1450 mL | 0.2900 mL | 0.7251 mL | |
| 50 mM | 0.0232 mL | 0.1160 mL | 0.2320 mL | 0.5801 mL | |
| 60 mM | 0.0193 mL | 0.0967 mL | 0.1934 mL | 0.4834 mL | |
| 80 mM | 0.0145 mL | 0.0725 mL | 0.1450 mL | 0.3626 mL | |
| 100 mM | 0.0116 mL | 0.0580 mL | 0.1160 mL | 0.2900 mL |
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