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| Targets |
The primary target of CCB02 is the interaction between CPAP (centrosomal P4.1-associated protein) and tubulin. By binding to β-tubulin, it competitively inhibits CPAP binding. This disrupts centrosome function and microtubule dynamics. CCB02 impairs proliferation of cells with centrosome amplification and causes cells to undergo centrosome de-clustering, prolonged multipolar mitosis, and cell death.
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| ln Vitro |
CCB02 inhibits the CPAP PN2-3-tubulin interaction in the PN2-3 CPAP-GST pull-down test, with an IC50 of 0.441 μM [1]. The phosphorylation status of Aurora A, Plk1, Plk2, CDK2, and CHK1 as well as centrosome-associated kinases are not inhibited by CCB02 [1]. Cancer cells with additional centrosomes are inhibited from proliferating by CCB02 (0.1-15 μM, 72 hours) with an IC50 of 0.86-2.9 μM [1]. CCB02 stimulates the recruitment of PCM proteins to the centrosome, activates the spindle assembly checkpoint, and increases the centrosome's microtubule nucleation activity [1].
In vitro, CCB02 is a selective CPAP-tubulin interaction inhibitor with an IC50 of 689 nM. It shows potent anti-tumor activity. It demonstrates broad anti-invasive activity in various cancer models, including tyrosine kinase inhibitor (TKI)-resistant EGFR-mutant NSCLC. Its activity is assessed by measuring cell proliferation, centrosome clustering, and mitotic progression. |
| ln Vivo |
CCB02 (30 mg/kg orally daily for 24 days) demonstrated strong anticancer effects in tumor xenografts of the human lung (H1975T790M cells) subcutaneously implanted in nude mice [1]. In mouse xenografts, CCB02 also results in multipolar mitosis and inhibits MDA-MB-231 cell migration [1].
In vivo, CCB02 (30 mg/kg, orally, daily for 24 days) shows potent anti-tumor effects in nude mice with subcutaneous human lung cancer (H1975 T790M cells) xenografts. This demonstrates its in vivo efficacy against a TKI-resistant cancer model. Its oral bioavailability and anti-tumor activity make it a promising candidate for cancer therapy. |
| Enzyme Assay |
For CPAP-tubulin binding assays, the interaction between CPAP and tubulin is measured using pull-down assays or fluorescence polarization. CCB02 is added to the reaction, and the inhibition of binding is measured. IC50 values are calculated. For cellular assays, the effect on cell proliferation, centrosome number, and mitotic progression is assessed.
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| Cell Assay |
Cell Viability Test[1]
Cell Types: BT549, MDA-MB-231, Pop10, SCC13, SW1271p53/pRb/CDKN2Adel, KYSE30p53/MYC/CyclinD1, A549G12S, PC-9EGFR-Exon19del, HCC827-GR, HCC1833-GR, H1975T790M Cell Tested Concentrations: 0.1-15 μM Incubation Duration: 72 hrs (hours) Experimental Results: IC50 is 0.86 μM (Pop10), 1.2 μM (HCC827-GR), 1.5 μM (H1975T790Mp53/MYC/CyclinD1), 1.15 μM (HCC1833-GR), 1.61 μM (SW1271p53/pRb/CDKN2Adel), 2.41 μM (SCC13) and 2.94 μM (PC-9EGFR-Exon19del). For cellular studies, cancer cells are cultured in appropriate medium. CCB02 is dissolved in DMSO and diluted in culture medium. Cells are treated with the compound. Cell viability is assessed by MTT or CellTiter-Glo assays. Centrosome number and mitotic spindle morphology are analyzed by immunofluorescence. Cell cycle and apoptosis are analyzed by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: Nude mice carrying subcutaneoushuman lung (H1975T790M) tumor xenografts [1]
Doses: 30 mg/kg Route of Administration: daily oral administration for 24 days Experimental Results: Tumor volume was Dramatically diminished on day 24. For in vivo efficacy studies, immunodeficient mice are implanted with cancer cells. CCB02 is formulated in vehicle and administered orally. Tumor growth is monitored. At study termination, tumors are excised and processed for analysis of centrosome number, mitotic index, and apoptosis markers. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for CCB02 are not extensively reported. As a small molecule, it is expected to have moderate oral bioavailability. Its metabolism likely involves hepatic CYP450 enzymes. A comprehensive PK study would be needed for any potential therapeutic development.
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| Toxicity/Toxicokinetics |
Toxicological data for CCB02 are limited. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
CCB02 (CAS 2100864-57-9) is a selective inhibitor of the CPAP-tubulin interaction with an IC50 of 689 nM. It has the molecular formula C₁₄H₉N₃O and a molecular weight of 235.24. It shows potent anti-tumor activity and is strictly for research use.
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| Molecular Formula |
C14H9N3O
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| Molecular Weight |
235.240762472153
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| Exact Mass |
235.074
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| CAS # |
2100864-57-9
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| PubChem CID |
129216797
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
350
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C)C1=C(C#N)C2C(C=N1)=CC1C=CC=CC=1N=2
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| InChi Key |
QNJYUHRGCPRPQS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H9N3O/c1-18-14-11(7-15)13-10(8-16-14)6-9-4-2-3-5-12(9)17-13/h2-6,8H,1H3
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| Chemical Name |
3-methoxybenzo[b][1,6]naphthyridine-4-carbonitrile
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~106.27 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (10.63 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2510 mL | 21.2549 mL | 42.5098 mL | |
| 5 mM | 0.8502 mL | 4.2510 mL | 8.5020 mL | |
| 10 mM | 0.4251 mL | 2.1255 mL | 4.2510 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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