CB039
Based on 1 Customer Validation
CB039 is a RBM39 molecular glue degrader with an IC50 of 36.7 nM against HCT-116 cells. CB039 induces RBM39 degradation in a dose- and time-dependent manner. This process depends on the Cullin-RING E3 ubiquitin ligase complex (CRL) and proteasome, and promotes the recruitment of RBM39 to the DCAF15-DDB1 complex with an IC50 of 594 nM. CB039 causes abnormal RNA splicing, reduces CEP192 protein levels, induces G2/M phase cell cycle arrest and mitotic spindle disorder. CB039 can be used in studies on RBM39-targeted protein degradation and colorectal cancer-related mechanisms.
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- Pureza: 98.10%
- No. CAS: 3056259-55-0
- Fòrmula: C23H23N5O5S
- Peso molecular:481.52
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Almacenamiento:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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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
Actividad biológica
Descripciòn
IC50 & Target
[1]|
RBM39 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | IC50 |
36.7 nM
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Antiproliferative activity against human HCT-116 colon cancer cells assessed as reduction in cell viability incubated for 4 days by Cell Counting Kit-8 assay.
Antiproliferative activity against human HCT-116 colon cancer cells assessed as reduction in cell viability incubated for 4 days by Cell Counting Kit-8 assay.
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40107850 |
In Vitro
CB039 (4 days) potently inhibits the proliferation of HCT-116 colon cancer cells, with an IC50 value of 36.7 nM[1].
CB039 (1 μM; 24 h) reduces the levels of at least 103 proteins by 2-fold or more in proteomic analysis of HCT-116 cells, among which RBM39 is the most significantly downregulated protein; CB039 also decreases the protein levels of CEP192, CENPI, KNL1 and RTTN in a dose-dependent manner[1].
CB039 (0.1 or 1 μM; 24 h) dose-dependently induces RBM39 degradation in HCT-116 cells, with the residual RBM39 level at 1 μM reaching approximately 21% of that in the vehicle control, while the DCAF15 protein level remains essentially unchanged[1].
CB039 (1 μM; 1-48 h) induces time-dependent degradation of RBM39 in HCT-116 cells. Obvious degradation is observed within 3-6 h and continues to increase up to 48 h[1].
CB039 displaces Probe-3 in a competitive fluorescence polarization assay containing RBM39, DCAF15-DDB1 and Probe-3, with an IC50 of 594 nM, which supports that CB039 promotes the recruitment of RBM39 to the DCAF15-DDB1 complex[1].
CB039 (1-10 μM; 12 h) induces abnormal RNA splicing in HCT-116 cells, leading to an approximately 3- to 30-fold increase in intron-retaining transcripts of CUL4A, NCKAP1L and PRPF38A, and an approximately 10-fold decrease in the normal exon 8-exon 9 transcript of ZNF207[1].
CB039 (0.1-10 μM; 12 h) dose-dependently induces CEP192 exon 42 skipping in HCT-116 cells; at 1 or 10 μM, it also increases CEP192 exon 42 skipping transcripts and decreases normal exon 41-42-43 transcripts in K562, MV4-11, HL-60, Kasumi-1, MOLM-13, CEM/C1 and RS4;11 cells[1].
CB039 (5 μM; 48 h) induces G2/M phase arrest in HCT-116 cells, increasing the proportion of G2/M phase cells to 60%; at 1 μM, it also exerts a time-dependent effect, with the proportions of G2/M phase cells reaching 33%, 58% and 66% at 24, 48 and 72 h, respectively[1].
CB039 (1 μM; 48 h) induces abnormal mitotic spindles and chromosome condensation/segregation failure in HCT-116 cells, reducing the proportion of normal mitotic cells to 0.8% and increasing the proportion of abnormal mitotic cells to 21.8%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT-116 colon cancer cells
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Concentration:1, 5, 10 μM
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Incubation Time:12 h
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Result:Increased intron-retaining CUL4A, NCKAP1L and PRPF38A transcripts and decreased normal ZNF207 transcripts.
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Cell Line:HCT-116 colon cancer cells
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Concentration:0.1-5 μM (48 h); 1 μM (24 h, 48 h, 72 h)
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Incubation Time:24 h, 48 h, 72 h
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Result:Increased the proportion of HCT-116 cells in the G2/M phase to 60% after treatment with 5 μM for 48 h.
Increased the G2/M phase fraction to 33% at 24 h, 58% at 48 h, and 66% at 72 h after treatment with 1 μM.
Induced negligible apoptosis after 48 h treatment.
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Cell Line:HCT-116 colon cancer cells
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Concentration:1 μM
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Incubation Time:48 h
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Result:Induced disorganized spindle structures, characterized by random microtubule distribution around condensed, undivided chromosomes.
Reduced the percentage of cells with normal mitosis to 0.8%, compared to 17.2% in the vehicle control group.
Increased the percentage of defective mitotic cells to 21.8%, compared to 0.3% in the vehicle control group.
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Cell Line:HCT-116 colon cancer cells
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Concentration:1 μM
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Incubation Time:1-48 h
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Result:Time-dependently degraded RBM39, with substantial degradation within 3-6 h.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC0-t |
|---|---|---|---|---|
| Mice[1] | 15 mg/kg | p.o. | 2120.77 ng/mL | 3482 |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 3-4 weeks old)[1]
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Dosage:50 mg/kg; 150 mg/kg
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Administration:p.o.; twice daily; 14 consecutive days (50 mg/kg); p.o.; once daily; 14 consecutive days (150 mg/kg)
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Result:Inhibited tumor growth by 72% compared to the vehicle group.
Chemical Information
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No. CAS 3056259-55-0
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Appearance Solid
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Peso molecular 481.52
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Fòrmula C23H23N5O5S
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Color White to off-white
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SMILES
CC1=C2C(NC=C2C#N)=C(C=C1)NS(C3=CC=CC(NC(C(N4[C@H](CCC4)CO)=O)=O)=C3)(=O)=O
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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
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (207.68 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 (sealed storage, away from moisture). 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). 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)
In Vivo:
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 (5.19 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.19 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
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. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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 (295 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). 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 | 2.0768 mL | 10.3838 mL | 20.7676 mL | 51.9189 mL |
| 5 mM | 0.4154 mL | 2.0768 mL | 4.1535 mL | 10.3838 mL | |
| 10 mM | 0.2077 mL | 1.0384 mL | 2.0768 mL | 5.1919 mL | |
| 15 mM | 0.1385 mL | 0.6923 mL | 1.3845 mL | 3.4613 mL | |
| 20 mM | 0.1038 mL | 0.5192 mL | 1.0384 mL | 2.5959 mL | |
| 25 mM | 0.0831 mL | 0.4154 mL | 0.8307 mL | 2.0768 mL | |
| 30 mM | 0.0692 mL | 0.3461 mL | 0.6923 mL | 1.7306 mL | |
| 40 mM | 0.0519 mL | 0.2596 mL | 0.5192 mL | 1.2980 mL | |
| 50 mM | 0.0415 mL | 0.2077 mL | 0.4154 mL | 1.0384 mL | |
| 60 mM | 0.0346 mL | 0.1731 mL | 0.3461 mL | 0.8653 mL | |
| 80 mM | 0.0260 mL | 0.1298 mL | 0.2596 mL | 0.6490 mL | |
| 100 mM | 0.0208 mL | 0.1038 mL | 0.2077 mL | 0.5192 mL |
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