CG428
Based on 1 Customer Validation
CG428 is a potent and selective CRBN-dependent tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 TPM3-TRKA fusion protein in KM12 colorectal carcinoma cells (DC50 = 0.36 nM) and inhibits downstream PLCγ1 phosphorylation (IC50 = 0.33 nM). CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively). CG428 can be used for the research of colorectal carcinoma.
(Pink: Trk Receptor ligand (HY-118271); Blue: Cereblon ligand (HY-41547); Black: linker (HY-W067489)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 98.18%
- No. CAS: 2412055-93-5
- Fòrmula: C43H43FN10O6
- Peso molecular:814.86
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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]|
TrkA 1 nM (Kd) |
TrkC 4.2 nM (Kd) |
TrkB 28 nM (Kd) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| KM12 | IC50 |
52 nM
Compound: 6; CG428
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Antiproliferative activity against human KM12 cells assessed as reduction in cell viability measured after 3 days by Celltiter-Glo assay
Antiproliferative activity against human KM12 cells assessed as reduction in cell viability measured after 3 days by Celltiter-Glo assay
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[PMID: 33058680] |
In Vitro
CG428 binds with high affinity to recombinant TRKA, TRKB, and TRKC kinases, with Kd values of 1.0, 28.0 and 4.2 nM[1].
CG428 degrades endogenous TPM3-TRKA fusion protein (DC50 = 0.36 nM) and inhibits PLCγ1 phosphorylation (IC50 = 0.33 nM) in KM12 cells[1].
CG428 potently degrades endogenous wild-type TRKA in HEL cells with a DC50 of 2.23 nM[1].
CG428 (0.7-500 nM; 6 h) exhibits reduced potency for degradation of ectopically expressed AGBL4-TRKB and ETV6-TRKC fusion protein in KM12 cells, with a hook effect at high concentrations[1].
CG428 potently inhibits the growth of KM12 cells with an IC50 of 2.9 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:KM12 human colorectal carcinoma cells
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Concentration:0.04, 0.12, 0.4, 1.1, 3.3, 10, 30 nM
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Incubation Time:6 h
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Result:Induced potent degradation of TPM3-TRKA with a DC50 of 0.36 ± 0.06 nM.
Inhibited downstream PLCγ1 phosphorylation with an IC50 of 0.33 ± 0.06 nM.
Caused 96 ± 3% TPM3-TRKA degradation at 10 nM.
Caused 82 ± 2% TPM3-TRKA degradation at 1 nM.
Caused 46 ± 6% TPM3-TRKA degradation at 0.1 nM.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | T1/2 |
|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 1640 nM | 1 h | 0.9 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (male)[1]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Reached a maximum plasma concentration of 1640 ± 120 nM at 1 h post dosing.
Plasma concentration was 12.4 ± 13.6 nM at 8 h post dosing.
Exhibited a half-life of 0.9 h.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 2412055-93-5
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Appearance Solid
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Peso molecular 814.86
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Fòrmula C43H43FN10O6
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Color Light yellow to yellow
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SMILES
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCCOCCC(N4CCN(C5=NC(C6=CN=C7C=CC(N8[C@@H](C9=CC=CC(F)=C9)CCC8)=NN76)=CC=C5)CC4)=O)=O
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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 : 100 mg/mL (122.72 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)
Protocolo
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
Pureza y Documentación
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Ficha de datos (272 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 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 | 1.2272 mL | 6.1360 mL | 12.2720 mL | 30.6801 mL |
| 5 mM | 0.2454 mL | 1.2272 mL | 2.4544 mL | 6.1360 mL | |
| 10 mM | 0.1227 mL | 0.6136 mL | 1.2272 mL | 3.0680 mL | |
| 15 mM | 0.0818 mL | 0.4091 mL | 0.8181 mL | 2.0453 mL | |
| 20 mM | 0.0614 mL | 0.3068 mL | 0.6136 mL | 1.5340 mL | |
| 25 mM | 0.0491 mL | 0.2454 mL | 0.4909 mL | 1.2272 mL | |
| 30 mM | 0.0409 mL | 0.2045 mL | 0.4091 mL | 1.0227 mL | |
| 40 mM | 0.0307 mL | 0.1534 mL | 0.3068 mL | 0.7670 mL | |
| 50 mM | 0.0245 mL | 0.1227 mL | 0.2454 mL | 0.6136 mL | |
| 60 mM | 0.0205 mL | 0.1023 mL | 0.2045 mL | 0.5113 mL | |
| 80 mM | 0.0153 mL | 0.0767 mL | 0.1534 mL | 0.3835 mL | |
| 100 mM | 0.0123 mL | 0.0614 mL | 0.1227 mL | 0.3068 mL |
CG428 Related Classifications
HY-137465 Related Classifications
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