BBI-2779
Based on 1 Customer Validation
BBI-2779 is a highly selective, orally active CHK1 inhibitor with a CHK1 IC50 of 0.3 nM. BBI-2779 leverages transcription-replication conflicts on extrachromosomal DNA (ecDNA) to induce synthetic lethality, replication stress, DNA damage and cell death in ecDNA-positive tumor cells. BBI-2779 blocks ecDNA-mediated acquired resistance to targeted therapies and inhibits tumor growth in mouse models of gastric cancer. BBI-2779 is applicable to ecDNA-positive cancer-related research.
For research use only. We do not sell to patients.
- Purity : 98.51%
- CAS No.: 2871057-47-3
- Formula: C19H19N7O2
- Molecular Weight:377.40
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Chk1 0.3 nM (IC50) |
In Vitro
BBI-2779 (3 days) is 10-fold more potent at inducing cytotoxicity in ecDNA-positive COLO320DM colorectal cancer cells (IC50 = 6 nM) compared to chromosomal amplification-positive COLO320HSR cells (IC50 = 60 nM)[2].
BBI-2779 (3-12 nM; 24 h) induces dose-dependent replication stress and DNA damage, measured via pCHK1-S345, pRPA2-S8, and γH2AX expression, preferentially in ecDNA-positive COLO320DM colorectal cancer cells compared to chromosomal amplification-positive COLO320HSR cells[2].
BBI-2779 selectively eliminates ecDNA-positive tumor cells by exploiting transcription-replication conflicts to induce synthetic lethality, and blocks ecDNA-mediated acquired resistance to targeted therapies in in vitro models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:COLO320DM (ecDNA-positive colorectal cancer cells), COLO320HSR (chromosomal amplification colorectal cancer cells)
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Concentration:14, 41, 123, 370, 1111 nM
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Incubation Time:16 h
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Result:Induced a dose-dependent increase in the percentage of cells with ≥3 phospho-RPA32 (S8) puncta (a replication stress biomarker).
Showed a significantly greater response in COLO320DM cells compared to COLO320HSR cells at all tested concentrations.
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Cell Line:COLO320DM (ecDNA-positive colorectal cancer cells), COLO320HSR (chromosomal amplification colorectal cancer cells)
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Concentration:3, 4, 6, 8, 12 nM
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Incubation Time:24 h
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Result:Induced a dose-dependent increase in pCHK1-S345, pRPA2-S8, and γH2AX (replication stress and DNA damage biomarkers) in COLO320DM cells.
Showed a substantially weaker response in COLO320HSR cells at equivalent concentrations.
Parmacokinetics
| Species | Dose | Route | CL | T1/2 | Tmax | Cmax | AUCinf | F |
|---|---|---|---|---|---|---|---|---|
| Mice[2] | 30 mg/kg | p.o. | 229 mL/min/kg | 1.11 h | 0.5 h | 713 ng/mL | 1568 ng·h/mL | 72 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:severe combined immunodeficient beige (female, 9 weeks old)[2]
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Dosage:30 mg/kg (single-agent); 30 mg/kg (combination with infigratinib 15 mg/kg)
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Administration:p.o.; every other day; 27 days (single-agent); p.o.; every other day; 27 days (combination with infigratinib p.o., once daily, 27 days)
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Result:Induced 64% tumour growth inhibition compared to vehicle-treated mice.
Resulted in significant tumour regression over the study duration when combined with infigratinib.
Suppressed adaptive FGFR2 oncogene copy number amplification on ecDNA (induced by single-agent infigratinib) when combined with infigratinib.
Increased expression of replication stress biomarkers pCHK1-S345 and pRPA2-S8 in tumour tissue compared to vehicle controls when combined with infigratinib.
Chemical Information
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CAS No. 2871057-47-3
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Appearance Solid
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Molecular Weight 377.40
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Formula C19H19N7O2
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Color White to light yellow
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SMILES
COC1=CC=CC(O[C@H]2[C@@H](CC2)N)=C1C3=CC(NC4=NC=C(C#N)N=C4)=NN3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (132.49 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)
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 (6.62 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.
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.
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.
Purity & Documentation
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Data Sheet (302 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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Handling Instructions (2659 KB)
References
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 | 2.6497 mL | 13.2485 mL | 26.4971 mL | 66.2427 mL |
| 5 mM | 0.5299 mL | 2.6497 mL | 5.2994 mL | 13.2485 mL | |
| 10 mM | 0.2650 mL | 1.3249 mL | 2.6497 mL | 6.6243 mL | |
| 15 mM | 0.1766 mL | 0.8832 mL | 1.7665 mL | 4.4162 mL | |
| 20 mM | 0.1325 mL | 0.6624 mL | 1.3249 mL | 3.3121 mL | |
| 25 mM | 0.1060 mL | 0.5299 mL | 1.0599 mL | 2.6497 mL | |
| 30 mM | 0.0883 mL | 0.4416 mL | 0.8832 mL | 2.2081 mL | |
| 40 mM | 0.0662 mL | 0.3312 mL | 0.6624 mL | 1.6561 mL | |
| 50 mM | 0.0530 mL | 0.2650 mL | 0.5299 mL | 1.3249 mL | |
| 60 mM | 0.0442 mL | 0.2208 mL | 0.4416 mL | 1.1040 mL | |
| 80 mM | 0.0331 mL | 0.1656 mL | 0.3312 mL | 0.8280 mL | |
| 100 mM | 0.0265 mL | 0.1325 mL | 0.2650 mL | 0.6624 mL |
BBI-2779 Related Classifications
HY-155798 Related Classifications
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