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| Targets |
Kinase inhibitor-1 targets the ErbB family of receptor tyrosine kinases, including EGFR (HER1) and HER2. It acts as an irreversible pan-ErbB inhibitor by covalently binding to a cysteine residue in the ATP-binding pocket of these kinases. By inhibiting NRG1 and suppressing HER2 mutants, the compound blocks downstream signaling pathways involved in cell proliferation and survival. This makes it a valuable tool for studying cancers driven by ErbB family alterations.
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| ln Vitro |
For many types of cancer, epidermal growth factor receptors (EGFR, HER1) present an appealing therapeutic target. An EGFR inhibitor with dose effectiveness is Tarlox-TKI [1].
In vitro, Kinase inhibitor-1 (Tarlox-TKI) is an irreversible pan-ErbB TKI that demonstrates antitumor activity. It inhibits NRG1 and suppresses HER2 mutants. For many types of cancer, epidermal growth factor receptors (EGFR, HER1) present an appealing therapeutic target, and Tarlox-TKI shows dose effectiveness as an EGFR inhibitor. The compound's irreversible binding mechanism provides sustained target inhibition. |
| ln Vivo |
In vivo studies of Kinase inhibitor-1 are focused on evaluating its antitumor efficacy in animal models of cancers driven by ErbB family alterations. As the bioactive metabolite of Tarloxotinib, it is generated from the hypoxia-activated prodrug in the tumor microenvironment. This hypoxia-activated approach is designed to enhance tumor selectivity and reduce systemic toxicity. Further in vivo studies are needed to fully characterize its efficacy, safety, and pharmacokinetic profile.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, Kinase inhibitor-1 can be evaluated using kinase activity assays that measure ErbB family kinase activity. The compound is incubated with recombinant EGFR or HER2 kinase and ATP at various concentrations. Kinase activity is quantified by measuring phosphorylation of peptide substrates using radiometric, fluorescence-based, or ELISA methods. IC₅0 values are determined from dose-response curves. The irreversible nature of inhibition can be confirmed by washout or dilution experiments.
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| Cell Assay |
For in vitro cellular experiments, Kinase inhibitor-1 is tested in cancer cell lines that express ErbB family receptors, such as those with EGFR mutations or HER2 amplification. Cells are cultured in appropriate media and treated with various concentrations of the compound. Cell viability, proliferation, and apoptosis are assessed using standard assays such as MTT, CellTiter-Glo, or flow cytometry. The compound's effects on downstream signaling pathways, such as MAPK and PI3K/AKT, are assessed by Western blotting.
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| Animal Protocol |
For in vivo animal experiments, Kinase inhibitor-1 can be administered to tumor-bearing mice via various routes, including intravenous injection or oral gavage. Xenograft models using human cancer cell lines with ErbB family alterations are commonly used to evaluate antitumor efficacy. Typical dosing regimens may range from 1 to 50 mg/kg. Tumor volume is measured regularly, and tumor growth inhibition is calculated. Pharmacodynamic markers, such as EGFR and HER2 phosphorylation, are assessed in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Kinase inhibitor-1 are not extensively detailed in the provided references. As a small molecule with a molecular weight of 461.74-461.75, it is likely to have reasonable bioavailability and tissue distribution. The compound is soluble in DMSO at 100 mg/mL. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies.
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| Toxicity/Toxicokinetics |
Toxicological data for Kinase inhibitor-1 are limited, as it is primarily a research tool. As an irreversible pan-ErbB inhibitor, its toxicity would depend on the importance of ErbB signaling for normal tissue homeostasis. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
Kinase inhibitor-1 is a research compound used to study ErbB family signaling and develop targeted cancer therapies. No clinical trials or regulatory approvals have been reported for this specific compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is the bioactive metabolite of Tarloxotinib and is an irreversible pan-ErbB inhibitor.
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| Molecular Formula |
C19H18BRCLN6O
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|---|---|
| Molecular Weight |
461.742821216583
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| Exact Mass |
460.041
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| CAS # |
2135696-72-7
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| PubChem CID |
51037658
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
551
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1=C(C=CC(=C1)NC1C2=CC(=NC=C2N=CN=1)NC(/C=C/CN(C)C)=O)Cl
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| InChi Key |
QBACGOWRJDBXSG-ONEGZZNKSA-N
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| InChi Code |
InChI=1S/C19H18BrClN6O/c1-27(2)7-3-4-18(28)26-17-9-13-16(10-22-17)23-11-24-19(13)25-12-5-6-15(21)14(20)8-12/h3-6,8-11H,7H2,1-2H3,(H,22,26,28)(H,23,24,25)/b4-3+
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| Chemical Name |
(E)-N-[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)but-2-enamide
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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 |
| 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 (~216.57 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.41 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 | 2.1657 mL | 10.8286 mL | 21.6572 mL | |
| 5 mM | 0.4331 mL | 2.1657 mL | 4.3314 mL | |
| 10 mM | 0.2166 mL | 1.0829 mL | 2.1657 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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