BBI-2779
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.
- CAS No.: 2871057-47-3
- Formula: C19H19N7O2
- Molecular Weight:377.40
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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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Help & FAQs
Biological Activity
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Chk1 0.3 nM (IC50) |
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].
BBI-2779 potently and selectively inhibits CHK1 in a cell-free biochemical assay with an IC50 of 0.3 nM and 160-fold selectivity over CHK2; it inhibited CHK1 activity, with an IC50 of 3 nM in HT29 cells[2].
BBI-2779 (14-1110 nM; 16 h) induces dose-dependent replication stress, measured via phospho-RPA32 (S8) puncta, preferentially in ecDNA-positive COLO320DM colorectal cancer cells compared to chromosomal amplification-positive COLO320HSR cells after 16 hours of treatment[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 (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].
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.
| 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 % |
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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Molecular Weight 377.40
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Formula C19H19N7O2
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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
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BBI-2779 Related Classifications
HY-155798 Related Classifications
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