HJM-561
Based on 1 Customer Validation
HJM-561 is a selective and effective orally active EGFR PROTAC degrader. HJM-561 is able to overcome the triple EGFR mutations that are resistant to Osimertinib (HY-15772). HJM-561 exhibits potent degradation of EGFR Del19/T790M/C797S (DC50: 9.2 nM) and L858R/T790M/C797S (DC50: 5.8 nM), and has anti-tumor activity (pink: EGFR ligand (HY-12857); blue: CRBN ligand (HY-A0003); black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.26%
- No. CAS: 2570251-68-0
- Fòrmula: C45H51ClN9O5P
- Peso molecular:864.37
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Almacenamiento:Powder -20°C, 3 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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
HJM-561 (0-300 nM, 24 h) potently degrades EGFR Del19/T790M/C797S (DC50: 9.2 nM) and L858R/T790M/C797S (DC50: 5.8 nM), but has no effect on wild-type EGFR[1].
HJM-561 (100 nM, 24 h) degrades the EGFR triple mutant in Del19/T790M/C797S Ba/F3 cells by activating CRBN E3 ligase and ubiquitin-proteasome system[1].
EGFR mutant, with IC50 of 15.6 and 17.0 nM in Del19/T790M/C797S cells and L858R/T790M/C797S cells, respectively[1].
EGFR expression (HEK293T and MDA-MB-231), indicating that it has no effect on cells expressing wild-type EGFR[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Del19/T790M/C797S-Ba/F3 cells
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Concentration:100 nM
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Incubation Time:24 h
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Result:Totally rescued EGFR degradation when Del19/T790M/C797S Ba/F3 cells were cotreated with the ubiquitination inhibitor MLN4924 (1 μM).
Failed to induce EGFR degradation in the presence of Pomalidomide (10 μM) in a competitive assay with the cereblon (CRBN) ligand.
HJM-561 (20, 40 mg/kg, p.o., once a day for 18 consecutive days) dose-dependently inhibits tumor growth in the human xenograft tumor (PDX) model, with a TGI of 67% at a dose of 40 mg/kg, and there is no significant change in mouse body weight[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:0.5 million EGFR Del19/T790M/C797S Ba/F3 cells and 50% Matrigel gel were subcutaneously inoculated in Balb/c nude mice (female aged 6-8 weeks)[1]
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Dosage:20, 40 mg/kg
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Administration:p.o., once a day for 18 consecutive days
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Result:Significantly reduced tumor volume by 58% and 84% at doses of 20 mg/kg and 40 mg/kg.
Showed that EGFR degradation and phosphorylated EGFR inhibition.
Chemical Information
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No. CAS 2570251-68-0
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Appearance Solid
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Peso molecular 864.37
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Fòrmula C45H51ClN9O5P
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Color Off-white to light yellow
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SMILES
O=C1C2=C(CN1C3C(NC(CC3)=O)=O)C(C#CCCN4CCN(C5CCN(CC5)C6=CC=C(C(OC)=C6)NC7=NC=C(C(NC8=C(P(C)(C)=O)C=CC=C8)=N7)Cl)CC4)=CC=C2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (115.69 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)
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 (2.89 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.
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 (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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Instrucciones de manejo (2659 KB)
Referencias
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 | 1.1569 mL | 5.7846 mL | 11.5691 mL | 28.9228 mL |
| 5 mM | 0.2314 mL | 1.1569 mL | 2.3138 mL | 5.7846 mL | |
| 10 mM | 0.1157 mL | 0.5785 mL | 1.1569 mL | 2.8923 mL | |
| 15 mM | 0.0771 mL | 0.3856 mL | 0.7713 mL | 1.9282 mL | |
| 20 mM | 0.0578 mL | 0.2892 mL | 0.5785 mL | 1.4461 mL | |
| 25 mM | 0.0463 mL | 0.2314 mL | 0.4628 mL | 1.1569 mL | |
| 30 mM | 0.0386 mL | 0.1928 mL | 0.3856 mL | 0.9641 mL | |
| 40 mM | 0.0289 mL | 0.1446 mL | 0.2892 mL | 0.7231 mL | |
| 50 mM | 0.0231 mL | 0.1157 mL | 0.2314 mL | 0.5785 mL | |
| 60 mM | 0.0193 mL | 0.0964 mL | 0.1928 mL | 0.4820 mL | |
| 80 mM | 0.0145 mL | 0.0723 mL | 0.1446 mL | 0.3615 mL | |
| 100 mM | 0.0116 mL | 0.0578 mL | 0.1157 mL | 0.2892 mL |
HJM-561 Related Classifications
HY-156698 Related Classifications
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