G-6599
Based on 1 Customer Validation
G-6599 is a covalent molecular glue degrader targeting SMARCA2/SMARCA4, with DC50 values of 0.017 nM and 0.057 nM against SMARCA2 and SMARCA4 in SW1573 cells, respectively. G-6599 exhibits proteome selectivity for SMARCA2, SMARCA4, and PBRM1. G-6599 induces the assembly of the SMARCA2-FBXO22 ternary complex, enabling ubiquitination and proteasomal degradation of both proteins via the ubiquitin-proteasome pathway without the need for biotransformation. G-6599 shows antiproliferative effects in relevant cancer cell models. G-6599 can be used for research on androgen-dependent prostate cancer and SMARCA4-mutant non-small cell lung cancer.
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- Pureza: 98.30%
- No. CAS: 2901806-51-5
- Fòrmula: C31H37N7O
- Peso molecular:523.67
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Almacenamiento:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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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
Descripciòn
IC50 & Target
[1]|
SMARCA2 0.017 nM (DC50) |
SMARCA4 0.057 nM (DC50) |
PBRM1 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SW1573 | DC50 |
0.017 nM
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Degradation of SMARCA2 in human SW1573 cells assessed via nuclear fluorescence intensity quantification after 18-hour incubation by high-throughput immunofluorescence degradation assay.
Degradation of SMARCA2 in human SW1573 cells assessed via nuclear fluorescence intensity quantification after 18-hour incubation by high-throughput immunofluorescence degradation assay.
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41184243 |
| SW1573 | DC50 |
0.057 nM
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Degradation of SMARCA4 in human SW1573 cells assessed via nuclear fluorescence intensity quantification after 18-hour incubation by high-throughput immunofluorescence degradation assay.
Degradation of SMARCA4 in human SW1573 cells assessed via nuclear fluorescence intensity quantification after 18-hour incubation by high-throughput immunofluorescence degradation assay.
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41184243 |
In Vitro
G-6599 (compound 6) (18 h) potently degrades SMARCA2 and SMARCA4 in SW1573 cells, with DC50 values of 0.017 nM and 0.057 nM, respectively[1].
G-6599-mediated degradation of SMARCA2 and SMARCA4 in SW1573 cells depends on the ubiquitin-proteasome pathway, cullin-RING ligase activity, and binding to the bromodomains of SMARCA2/A4[1].
G-6599 (100 nM; 30 min) induces specific ubiquitination of SMARCA2, SMARCA4 and PBRM1 in SW1573 cells without altering the ubiquitination levels of other cellular proteins[1].
G-6599 (100 nM; 3 h) selectively depletes SMARCA2, SMARCA4 and PBRM1 in SW1573 cells, with no off-target effects detected at the global proteome level[1].
G‑6599 requires the ligase activity of FBXO22 together with cysteine residues C228 and C326 for efficient SMARCA2 degradation in HCC515 cells; G‑6599 mediates the physical interaction between FBXO22/SKP1 and the bromodomain of SMARCA2 in vitro[1].
G-6599 (4-333 nM; overnight) induces the formation of a dose-dependent ternary complex between SMARCA2 and FBXO22 in FBXO22-knockout HCC515 cells[1].
G-6599 (100 µM; 1 min to 2280 min) induces conformational changes in FBXO22, thereby enhancing its interaction with the bromodomain of SMARCA2, and this effect is particularly pronounced in the FIST domain region near Cys326[1].
G-6599 (20 µM; 4 h) forms covalent adducts with FBXO22 in vitro, and adduct formation is observed even in the absence of the SMARCA2 bromodomain at high concentrations[1].
G-6599 (50 µM; 4 h) covalently modifies multiple cysteine residues on FBXO22 in vitro, and Cys228 serves as the primary modification site when incubated with the SMARCA2 bromodomain[1].
G-6599 (7 days) inhibits the growth of SMARCA4G12C-mutant non-small cell lung cancer and androgen receptor (AR)-dependent prostate cancer cells, exhibits reduced activity in normal prostate epithelial cells, and shows no activity in SMARCA2/A4-deficient NCI-H522 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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No. CAS 2901806-51-5
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Appearance Solid
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Peso molecular 523.67
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Fòrmula C31H37N7O
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Color White to light yellow
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SMILES
OC1=CC=CC=C1C2=CC(N3CC4N(C5=CC(C#CCCN6CCCCCC6)=NC=C5)C(CC4)C3)=C(N)N=N2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvente y solubilidad
In Vitro:
DMSO : ≥ 100 mg/mL (190.96 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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 (sealed storage, away from moisture and light). 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 (sealed storage, away from moisture and light). 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 (283 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 (sealed storage, away from moisture and light). 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 | 1.9096 mL | 9.5480 mL | 19.0960 mL | 47.7400 mL |
| 5 mM | 0.3819 mL | 1.9096 mL | 3.8192 mL | 9.5480 mL | |
| 10 mM | 0.1910 mL | 0.9548 mL | 1.9096 mL | 4.7740 mL | |
| 15 mM | 0.1273 mL | 0.6365 mL | 1.2731 mL | 3.1827 mL | |
| 20 mM | 0.0955 mL | 0.4774 mL | 0.9548 mL | 2.3870 mL | |
| 25 mM | 0.0764 mL | 0.3819 mL | 0.7638 mL | 1.9096 mL | |
| 30 mM | 0.0637 mL | 0.3183 mL | 0.6365 mL | 1.5913 mL | |
| 40 mM | 0.0477 mL | 0.2387 mL | 0.4774 mL | 1.1935 mL | |
| 50 mM | 0.0382 mL | 0.1910 mL | 0.3819 mL | 0.9548 mL | |
| 60 mM | 0.0318 mL | 0.1591 mL | 0.3183 mL | 0.7957 mL | |
| 80 mM | 0.0239 mL | 0.1193 mL | 0.2387 mL | 0.5967 mL | |
| 100 mM | 0.0191 mL | 0.0955 mL | 0.1910 mL | 0.4774 mL |
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