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| 25mg |
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Purity: ≥98%
Avitinib maleate (formerly also known as AC-0010, AC0010MA; Abivertinib), the maleate salt of avitinib, is an orally bioavailable and covalent/irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. It has anticancer activity and currently in clinical trials. AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib.
| ln Vitro |
In NCI-H1975 and NIH/3T3_TC32T8 cells, avitinib (AC0010; 0.13 nM-2 μM; 2 h) maleate selectively inhibits the phosphorylation of mutant EGFR with IC50 values of 7.3 and 2.8 nM, respectively. These values are approximately 115 and 298 times more sensitive than inhibition. EGFR times wild-type in A431. In NCI-H1975 cells, avitinib efficiently inhibits EGFR-Tyr1068 phosphorylation, and NCI-H1975 cells have 65 times greater selectivity than A431 cells. Apart from preventing EGFR-Tyr1068 phosphorylation, avitinib also prevents Akt and ERK1/2, which are downstream targets, from becoming phosphorylated in NCI-H1975 and HCC827 cells [1].
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| ln Vivo |
In xenograft models, long-term avitinib (AC0010; 12.5-500 mg/kg; oral; once daily; for 14 days) slows the growth of EGFR mutant tumors but not wild-type EGFR tumors [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: NCI-H1975, HCC827, A431 cells Tested Concentrations: 0.13 nM, 0.64 nM, 3.2 nM, 16 nM, 80 nM, 0.4 μM, 2 μM Incubation Duration: 2 h Experimental Results: Selectively inhibits mutant EGFR phosphorylation with IC50 values of 7.3 and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells. |
| Animal Protocol |
Animal/Disease Models: Nu/Nu nude mice (Six- to 8weeks old) injected with NCI-H1975 and A431 cells[1]
Doses: 12.5, 50, and 500 mg/kg Route of Administration: Orally administration; one time/day; for 14 days Experimental Results: Inhibited EGFR-mutant tumor growth but not wild-type EGFR tumor growth. |
| 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.
[2]. Yan X, et al. Promising efficacy of novel BTK inhibitor AC0010 in mantle cell lymphoma. J Cancer Res Clin Oncol. 2018;144(4):697-706. |
| Molecular Formula |
C30H30FN7O6
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| Molecular Weight |
603.61
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| CAS # |
1557268-88-8
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| Related CAS # |
Avitinib;1557267-42-1
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| SMILES |
FC1C([H])=C(C([H])=C([H])C=1N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C1N=C(C2C([H])=C([H])N([H])C=2N=1)OC1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C([H])=C([H])[H])=O.O([H])C(/C(/[H])=C(/[H])\C(=O)O[H])=O
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 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 (4.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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: ≥ 2.5 mg/mL (4.14 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 | 1.6567 mL | 8.2835 mL | 16.5670 mL | |
| 5 mM | 0.3313 mL | 1.6567 mL | 3.3134 mL | |
| 10 mM | 0.1657 mL | 0.8283 mL | 1.6567 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.
Response of NSCLC patients with T790M-acquired mutations to AC0010 treatment and their AC0010 plasma concentrations. |
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Inhibition of cell proliferation and EGFR phosphorylation.Mol Cancer Ther.2016 Nov;15(11):2586-2597. |
In vivoantitumor efficacy and pharmacokinetics/pharmacodynamics in xenograft models.Mol Cancer Ther.2016 Nov;15(11):2586-2597. |
Proposed AC0010 metabolic pathways and activities of its major metabolites.Mol Cancer Ther.2016 Nov;15(11):2586-2597. |
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 AC0010 chemical structure and T790M EGFR-binding modes.Mol Cancer Ther.2016 Nov;15(11):2586-2597. |
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