Avitinib maleate |
| Katalog-Nr.GC19044 |
Avitinib (Abivertinib) Maleat ist ein auf Pyrrolopyrimidin basierender irreversibler epidermaler Wachstumsfaktorrezeptor (EGFR)-Inhibitor mit einem IC50 von 7,68 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1557268-88-8
Sample solution is provided at 25 µL, 10mM.
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Avitinib maleate is a pyrrolopyrimidine-based irreversible epidermal growth factor receptor (EGFR) inhibitor with an IC50 of 7.68 nM.
Avitinib is structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors such as osimertinib and rociletinib. Avitinib is designed specifically to inhibit EGFR active mutations and the T790M acquired resistant mutation, while sparing wild type EGFR. Avitinib selectively inhibits EGFR active and T790M mutations with up to 298-fold increase in potency compared to wild-type EGFR. Avitinib exhibits potent inhibitory activity with IC50 value of 0.18 nM against EGFR L858R/T790M double mutations, nearly 43-fold greater potency over wild-type EGFR (IC50=7.68 nM). Avitinib selectively inhibits mutant EGFR phosphorylation with IC50 values of 7.3 nM and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells, about 115- and 298-fold more sensitive than that of the inhibition of wild type EGFR in A431[1].
Oral administration of avitinib at daily dose of 500 mg/kg results in complete remission of tumors with EGFR active and T790M mutations for over 143 days with no weight loss. Three major metabolites of avitinib are tested and show no wild-type EGFR inhibition and off-target effects such as inhibition of IGF-1R. Avitinib is safe in non-small cell lung cancer (NSCLC) patients at the dose range between 50 mg and 550 mg once per day and no hyperglycemia and other severe adverse effects are detected such as grade 3 QT prolongation[1].
References:
[1]. Xu X, et al. AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients. Mol Cancer Ther. 2016 Nov;15(11):2586-2597.
Cell experiment: | Cell proliferation is assayed by a cell viability reagent, WST-1. Cells are seeded at optimal density onto 96-well plates and incubated for 24 hours, followed by avitinib treatment for 72 hours. Cell viability is then assayed by incubating cells with WST-1 reagent for 2-3 hrs[1]. |
Animal experiment: | Rats: To assess the potential skin toxicity of avitinib, a rat model is used. Rats are administrated daily with avitinib at 300 mg/kg for 4 weeks, and in control groups gefitinib at 50mg/kg or vehicle control (0.5% MC) is administrated[1]. Mice: NCI-H1975 tumor bearing mice are orally treated with a vehicle control (0.5% MC), avitinib at dose levels of 12.5 mg/kg and 50 mg/kg for 17 days when TV value in vehicle control group reached approximately 2000 mm3 . After 17-day dosing, animals in the vehicle control group are sacrificed, whereas animals in avitinib groups are continually daily administrated with increased dose at 500 mg/kg till the test mice cannot tolerate the treatment. Mouse body weight and TV are measured twice per week. TV is then used for the calculation of tumor inhibitory rate and tumor regression rate[1]. |
References: [1]. Xu X, et al. AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients. Mol Cancer Ther. 2016 Nov;15(11):2586-2597. | |
| Cas No. | 1557268-88-8 | SDF | |
| Canonical SMILES | O=C(O)/C=C\C(O)=O.O=C(C=C)NC1=CC=CC(OC2=NC(NC3=CC(F)=C(N4CCN(C)CC4)C=C3)=NC5=C2C=CN5)=C1 | ||
| Formula | C30H30FN7O6 | M.Wt | 603.6 |
| Löslichkeit | DMSO : ≥ 300 mg/mL (497.02 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6567 mL | 8.2836 mL | 16.5673 mL |
| 5 mM | 0.3313 mL | 1.6567 mL | 3.3135 mL |
| 10 mM | 0.1657 mL | 0.8284 mL | 1.6567 mL |
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μL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 2 reference(s) in Google Scholar.)
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