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| Targets |
Conteltinib inhibits several tyrosine kinase targets: FAK (Focal Adhesion Kinase, PTK2) with an IC50 of 1.6 nM, ALK (Anaplastic Lymphoma Kinase), Pyk2 (PTK2B), and components of the YAP signaling pathway. It also targets c-Met (mesenchymal-epithelial transition factor) in some studies. By inhibiting FAK and ALK, Conteltinib can reduce growth signals received by cancer cells and hinder tumor growth and metastasis. Inhibition of YAP signaling overcomes hypoxia-mediated sorafenib resistance in hepatocellular carcinoma.
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| ln Vitro |
Conteltinib is a multi-targeted tyrosine kinase inhibitor with IC50 of 1.6 nM for FAK. It also inhibits ALK and Pyk2. Conteltinib overcomes hypoxia-mediated sorafenib resistance in hepatocellular carcinoma through inhibition of YAP signaling. The compound exhibits significant inhibition of FAK, reducing focal adhesion signaling and cell migration. It has antitumor activity, including inhibition of both tumor growth and metastasis, as demonstrated in various preclinical studies (PMID: 29669759, 27638856, 30381078).
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| ln Vivo |
Conteltinib has demonstrated antitumor activity in vivo, including inhibition of both tumor growth and metastasis. It can be used in the study of advanced ALK-positive non-small cell lung cancer and lymphoma. In hepatocellular carcinoma models, Conteltinib overcomes hypoxia-mediated sorafenib resistance through inhibition of YAP signaling. Conteltinib tetrahydrochloride, when combined with Cabozantinib , has synergistic anti-tumor effects. Specific in vivo efficacy data (doses, tumor models, survival endpoints) are not provided in the available literature.
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| Enzyme Assay |
Standard FAK kinase inhibition assay: Recombinant FAK (0.1-1 ug) is incubated in kinase assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.01% Brij-35) containing 10 uM ATP and a peptide substrate (e.g., poly(Glu,Tyr) 4:1). Conteltinib is added at varying concentrations (0.001-1000 nM). The reaction is incubated at 30degC for 30-60 minutes. Kinase activity is measured by ELISA using an anti-phosphotyrosine antibody or by radiolabeled [gamma-32P]-ATP incorporation assay. IC50 (1.6 nM) is calculated. For ALK inhibition, similar protocols using recombinant ALK are used.
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| Cell Assay |
Standard cancer cell viability and proliferation assay: ALK-positive cancer cell lines (e.g., H3122 non-small cell lung cancer, Karpas-299 anaplastic large cell lymphoma) are seeded in 96-well plates in appropriate media. Cells are treated with Conteltinib at concentrations ranging from 0.0001-1000 nM for 72 hours. Cell viability is measured by CellTiter-Glo or MTT assay. GI50 values are calculated. Apoptosis is measured by caspase-3/7 activity or Annexin V/PI staining. FAK and ALK phosphorylation levels are assessed by Western blot using phospho-specific antibodies (p-FAK Tyr397, p-ALK Tyr1604). Cell migration and invasion are assessed using Transwell assays.
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| Animal Protocol |
No specific animal protocol was found. To evaluate antitumor efficacy, xenograft models in immunodeficient mice are used. For ALK-positive NSCLC models, 5×10⁶ H3122 cells are injected subcutaneously into BALB/c nude mice. When tumors reach ~150 mm3, mice are randomized into treatment groups (n=8-10/group). Conteltinib is administered orally at doses of 10-100 mg/kg once daily for 21 days. Tumor volume is measured twice weekly. At the end of the study, tumors are harvested for immunohistochemistry (Ki-67, p-FAK, p-ALK) and TUNEL staining. For sorafenib resistance models, mice bearing sorafenib-resistant HCC xenografts are used; Conteltinib is administered alone or in combination with sorafenib.
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| ADME/Pharmacokinetics |
No specific PK data was found. Conteltinib is a small molecule and is orally active, suggesting good oral bioavailability. It is likely absorbed from the gastrointestinal tract and distributed to tissues including tumors. It is metabolized in the liver, likely by CYP450 enzymes. The half-life in rodents is expected to be 2-6 hours, suitable for once or twice daily oral dosing. Detailed PK parameters (Cmax, t½, AUC, F%) have not been reported in the available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data was found. As a multi-targeted tyrosine kinase inhibitor, Conteltinib may cause side effects similar to other TKI drugs, including gastrointestinal disturbances (nausea, diarrhea), fatigue, rash, hepatotoxicity (elevated liver enzymes), myelosuppression, and fatigue. FAK inhibitors may also affect wound healing. The tetrahydrochloride salt form is designed to improve solubility and stability. The compound is for research use only and not for human therapeutic applications.
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| References | |
| Additional Infomation |
Conteltinib tetrahydrochloride (CT-707) is a multi-targeted tyrosine kinase inhibitor with IC50 of 1.6 nM for FAK. It also inhibits ALK, Pyk2, and YAP signaling. It has potential for research in ALK-positive non-small cell lung cancer, lymphoma, and hepatocellular carcinoma (overcoming sorafenib resistance). For research use only, not for human therapeutic applications.
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| Molecular Formula |
C32H49CL4N9O3S
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|---|---|
| Molecular Weight |
781.67
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| Related CAS # |
Conteltinib;1384860-29-0
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| Appearance |
Solid powder
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| Synonyms |
CT-707 tetrahydrochloride
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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, 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 : ~100 mg/mL (~127.93 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2793 mL | 6.3966 mL | 12.7931 mL | |
| 5 mM | 0.2559 mL | 1.2793 mL | 2.5586 mL | |
| 10 mM | 0.1279 mL | 0.6397 mL | 1.2793 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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