| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Simotinib targets the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that is commonly mutated in non-small cell lung cancer (NSCLC). By inhibiting EGFR tyrosine kinase activity, simotinib blocks downstream signaling pathways (such as RAS-RAF-MEK-ERK and PI3K-AKT) that promote cancer cell proliferation and survival. It is a selective and specific EGFR inhibitor.
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| ln Vitro |
Cimotinib shows no discernible action against other kinases under investigation, although it dose-dependently suppresses EGFR and the proliferation of human A431 tumor cells that overexpress EGFR [1].
Simotinib inhibits EGFR tyrosine kinase activity with an IC50 of 19.9 nM. In preclinical studies, simotinib has demonstrated equal or superior antineoplastic activities to erlotinib. The compound shows potent antiproliferative activity against EGFR-mutant cancer cell lines, consistent with its mechanism of action. |
| ln Vivo |
In nude xenograft models, it has been demonstrated that imatinib inhibits EGFR phosphorylation, hence exerting anti-tumor action [1].
Simotinib has demonstrated in vivo efficacy in preclinical models of EGFR-mutant NSCLC. In xenograft models, simotinib administered orally produces dose-dependent tumor growth inhibition. The compound has shown equal or superior antitumor activity compared to erlotinib. Simotinib represents a potential targeted treatment option for patients with EGFR-mutant NSCLC. |
| Enzyme Assay |
EGFR tyrosine kinase activity is assessed using in vitro kinase assays with purified recombinant EGFR (wild-type or mutant) and a peptide substrate. The assay measures the incorporation of [γ-³²P]-ATP into the substrate or uses a luminescent ADP detection method. Simotinib is incubated at various concentrations, and IC50 values are calculated from dose-response curves. Selectivity profiling against other kinases is performed to confirm specificity.
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| Cell Assay |
Cellular activity is evaluated in EGFR-mutant NSCLC cell lines. Cells are treated with simotinib at various concentrations for 48-72 hours, and cell viability is measured using MTT, XTT, or CellTiter-Glo assays. IC50 values for proliferation inhibition are calculated. Inhibition of EGFR phosphorylation (p-EGFR) and downstream signaling (p-ERK, p-AKT) is assessed by Western blot or phospho-specific ELISA.
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| Animal Protocol |
Simotinib is administered orally to mice bearing EGFR-mutant NSCLC xenografts. Tumor-bearing mice are treated with simotinib at various doses (e.g., 10-50 mg/kg) on a daily schedule. Tumor volumes are measured twice weekly, and body weight is monitored. Efficacy is compared to vehicle and positive control (e.g., erlotinib) groups. Pharmacodynamic studies may include measurement of p-EGFR levels in tumor tissue.
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| ADME/Pharmacokinetics |
Simotinib has a molecular weight of 500.95 and molecular formula C25H26ClFN4O4. The IUPAC name is 6-(2-(5,8-Dioxa-10-azadispiro[2.0.44.33]undecan-10-yl)ethoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine. The compound is orally bioavailable and is soluble in DMSO. Simotinib is also known as SIM6802. It is a small-molecule EGFR tyrosine kinase inhibitor.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of simotinib have shown that it is tolerated at therapeutic doses. As an EGFR inhibitor, mechanism-based toxicities may include skin rash and gastrointestinal effects, which are common to this class of drugs. In animal models, simotinib has been used at various doses without significant adverse effects reported. Further toxicological characterization is needed for clinical development.
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| References | |
| Additional Infomation |
Simotinib (CAS#: 944258-89-3) is a selective, specific, and orally bioavailable EGFR tyrosine kinase inhibitor with an IC50 of 19.9 nM. It is also known as SIM6802. Simotinib targets EGFR mutations commonly associated with NSCLC and has demonstrated equal or superior antineoplastic activities to erlotinib in preclinical studies. It represents a potential targeted treatment option for patients with EGFR-mutant NSCLC. Simotinib is intended for research use only.
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| Molecular Formula |
C25H26CLFN4O4
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|---|---|
| Molecular Weight |
500.949748516083
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| Exact Mass |
500.162
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| CAS # |
944258-89-3
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| Related CAS # |
Simotinib hydrochloride;1538617-88-7
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| PubChem CID |
16735117
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
640.0±55.0 °C at 760 mmHg
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| Flash Point |
340.8±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.669
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| LogP |
3.96
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
742
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OXWUWXCJDBRCCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H26ClFN4O4/c1-32-21-12-20-17(23(29-15-28-20)30-16-2-3-19(27)18(26)10-16)11-22(21)33-7-6-31-13-24(4-5-24)25(14-31)34-8-9-35-25/h2-3,10-12,15H,4-9,13-14H2,1H3,(H,28,29,30)
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| Chemical Name |
N-(3-chloro-4-fluorophenyl)-6-(2-(5,8-dioxa-11-azadispiro(2.0.4.3)undec-11-yl)ethoxy)-7-methoxy-4-quinazolinamine
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| Synonyms |
SIM6802 SIM 6802 SIM6802
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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 : ~125 mg/mL (~249.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.15 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 20.8 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: 2.08 mg/mL (4.15 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9962 mL | 9.9810 mL | 19.9621 mL | |
| 5 mM | 0.3992 mL | 1.9962 mL | 3.9924 mL | |
| 10 mM | 0.1996 mL | 0.9981 mL | 1.9962 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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