DS03090629
Based on 1 Customer Validation
DS03090629 is an orally active, ATP-competitive MEK1/2 inhibitor. DS03090629 binds to the ATP-binding pocket of MEK, and this binding is unaffected by phosphorylation status. DS03090629 exhibits high affinity for both MEK and phosphorylated MEK, with Kd values of 0.11 nM and 0.15 nM, respectively. DS03090629 inhibits the MEK1F53L mutant while retaining activity relative to wild-type MEK1. DS03090629 suppresses the MAPK pathway, cell proliferation, and BRAF overexpression-mediated drug resistance in melanoma cells. DS03090629 can be used for research related to melanoma.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.16%
- Fòrmula: C25H26ClN5O2
- Peso molecular:463.96
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Almacenamiento: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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
MEK1 |
MEK2 |
In Vitro
DS03090629 (0.5 mM; 48 h) binds to the ATP-binding pocket of human MEK1 (residues 37-383 with MEK1S298N, MEK1S299K, MEK1Y300K mutations) as visualized via X-ray crystallography[1].
DS03090629 (1-10000 nM; 60 min) potently inhibits kinase activity of both wild-type phosphorylated MEK1 and phosphorylated MEK1F53L mutant in a cell-free assay[1].
DS03090629 (0.001-10000 nM) potently inhibits both non-phosphorylated and phosphorylated MEK1 kinase activity in in vitro assays, with minimal difference in efficacy between the two protein forms[1].
DS03090629 (3.2-2000 nM) maintains high binding affinity for both non-phosphorylated and phosphorylated human MEK1, with a KD of 0.1086 nM for npMEK1 and 0.1497 nM for pMEK1[1].
DS03090629 (350 nM) exhibits high selectivity for MEK1/2 over a panel of 159 other kinases when tested at 350 nM in the presence of 1 mM ATP[1].
DS03090629 (0.1-10000 nM; 2 h) inhibits ERK phosphorylation with IC50 values of 37.1 nM in A375_mock cells, 74.3 nM in BRAF-overexpressing A375_BRAF cells, and 95.3 nM in HUVEC cells, with minimal potency reduction in the resistant cell line[1].
DS03090629 (0.1-10000 nM; 3 day) inhibits cell proliferation with IC50 values of 60.7 nM in A375_mock cells, 165 nM in BRAF-overexpressing A375_BRAF cells, and 556 nM in HUVEC cells, with minimal potency reduction in the resistant cell line[1].
DS03090629 (0.1-10000 nM; 2 h) inhibits ERK phosphorylation in MEK1F53L-expressing A375_MEK cells with an IC50 of 97.8 nM, with minimal potency reduction relative to parental A375_mock cells[1].
DS03090629 (0.1-10000 nM 3 day) inhibits cell proliferation in MEK1F53L-expressing A375_MEK cells with an IC50 of 165 nM, with minimal potency reduction relative to parental A375_mock cells[1].
DS03090629 (0.1-10000 nM; 2 h) retains relatively potent ERK phosphorylation inhibitory activity in NRASQ61K-expressing A375_NRAS cells compared to other tested inhibitors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A375_mock, A375_BRAF, HUVEC cells
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Concentration:0.1-10000 nM
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Incubation Time:3 day
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Result:Inhibited cell proliferation with IC50 values of 60.7 nmol/L in A375_mock, 165 nmol/L in A375_BRAF, and 556 nmol/L in HUVEC.
The A375_BRAF/A375_mock IC50 ratio was 2.72, showing reduced potency attenuation in the resistant line compared to trametinib.
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Cell Line:A375_MEK (MEK1 F53L-expressing melanoma) cells
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Concentration:0.1-10000 nM
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Incubation Time:3 day
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Result:Inhibited cell proliferation in A375_MEK cells with an IC50 of 165 nmol/L, with an A375_MEK/A375_mock IC50 ratio of 3.20, showing reduced potency attenuation compared to trametinib.
In Vivo
DS03090629 (75 mg/kg; p.o.; once daily) alone shows modest tumor growth inhibition, while its combination with Dabrafenib (100 mg/kg; p.o.; twice daily) significantly inhibits tumor growth and ERK phosphorylation in BRAFV600E-overexpressing A375_BRAF melanoma xenografts resistant to standard BRAF/MEK inhibitor therapy[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CAnN.Cg-Foxn1(nu)/CrlCrlj (Foxn1nu/Foxn1nu) (female, 4 to 5-weeks-old)[1]
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Dosage:75 mg/kg (single agent); 75 mg/kg (in combination with dabrafenib 100 mg/kg)
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Administration:p.o.; once daily; p.o.; twice daily (dabrafenib)
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Result:Achieved tumor stasis as a single agent.
Induced tumor regression when combined with dabrafenib, with statistically significant reductions in tumor volume and weight relative to vehicle control on final day of administration.
Significantly inhibited ERK phosphorylation in A375mock tumors at a single dose alone.
Produced significant ERK phosphorylation inhibition when combined with dabrafenib.\nExhibited 18% tumor growth inhibition, which was modest and non-statistically significant, as a single agent.
Significantly inhibited tumor growth when combined with dabrafenib, with statistically significant reductions in tumor volume and weight relative to vehicle control on final day of administration.
Did not inhibit ERK phosphorylation in A375_BRAF tumors at a single dose alone.
Produced significant ERK phosphorylation inhibition when combined with dabrafenib.
- Western Blot
- BrdU Incorporation Assay
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Protocol for Kinase activity and phosphorylation assays
- MTT Cell Proliferation Assay
Chemical Information
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Appearance Solid
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Peso molecular 463.96
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Fòrmula C25H26ClN5O2
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Color White to off-white
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SMILES
CC1=NNC2=CC(C3=CC=C(OC4=NC=CC(C)=N4)C=C3Cl)=CC(O[C@@H]5C[C@H](N)CCC5)=C21
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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 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (107.77 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)
Pureza y Documentación
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Ficha de datos (278 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 |
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| DMSO | 1 mM | 2.1554 mL | 10.7768 mL | 21.5536 mL | 53.8840 mL |
| 5 mM | 0.4311 mL | 2.1554 mL | 4.3107 mL | 10.7768 mL | |
| 10 mM | 0.2155 mL | 1.0777 mL | 2.1554 mL | 5.3884 mL | |
| 15 mM | 0.1437 mL | 0.7185 mL | 1.4369 mL | 3.5923 mL | |
| 20 mM | 0.1078 mL | 0.5388 mL | 1.0777 mL | 2.6942 mL | |
| 25 mM | 0.0862 mL | 0.4311 mL | 0.8621 mL | 2.1554 mL | |
| 30 mM | 0.0718 mL | 0.3592 mL | 0.7185 mL | 1.7961 mL | |
| 40 mM | 0.0539 mL | 0.2694 mL | 0.5388 mL | 1.3471 mL | |
| 50 mM | 0.0431 mL | 0.2155 mL | 0.4311 mL | 1.0777 mL | |
| 60 mM | 0.0359 mL | 0.1796 mL | 0.3592 mL | 0.8981 mL | |
| 80 mM | 0.0269 mL | 0.1347 mL | 0.2694 mL | 0.6735 mL | |
| 100 mM | 0.0216 mL | 0.1078 mL | 0.2155 mL | 0.5388 mL |
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