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| 5mg |
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| 100mg |
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Purity: ≥98%
Avitinib (Abivertinib, AC-0010, AC-0010MA, AC0010, AC0010MA) is a pyrrolopyrimidine-based, orally bioactive, and irreversible/covalent inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with selectivity against T790M resistance mutations. Avitinib differs structurally from other known irreversible EGFR inhibitors based on pyrimidines, such as rociletinib and osimertinib.
| Targets |
EGFR L858R (IC50 = 0.18 nM); EGFRT790M (IC50 = 0.18 nM); EGFR (WT) (IC50 = 7.68 nM)
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| ln Vivo |
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| Enzyme Assay |
Reaction Biology Corp., a service provider, carried out the kinase activity assay (Malvern, PA, USA). AC0010 was utilized at a concentration of either 1 µM or 10 µM for the single dose screening assay. A 10-concentration gradient from 5.1x10-11-1.0x10-6 mol/L was set for the tested compounds in order to determine their IC50 values. In order to assess the assay quality for one-dose kinase activity assays and IC50 value calculations, staurosporine was used as a control compound.
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| Cell Assay |
The cell viability reagent WST-1 was used to measure the proliferation of cells. After being optimally densely seeded onto 96-well plates, the cells underwent a 24-hour incubation period and a 72-hour compound treatment period. Next, cells were cultured with WST-1 reagent for two to three hours in order to test the viability of the cells.
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| Animal Protocol |
Nu/Nu nude mice
12.5 mg/kg, 50 mg/kg and 500 mg/kg oral |
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| References | ||
| Additional Infomation |
Abivertinib is a tyrosine kinase inhibitor targeted against mutant forms of both human epidermal growth factor receptor (EGFR) and Bruton's tyrosine kinase (BTK). It has been investigated for use in the treatment of non-small cell lung cancer (NSCLC) and B-cell malignancies. In binding to and inhibiting EGFR and BTK receptors, abivertinib exerts immunomodulatory effects by preventing the production and release of pro-inflammatory cytokines (e.g. TNF-alpha, interleukins). Abivertinib's potential to depress cytokine production has led to its investigation in the treatment of hospitalized patients with moderate-to-severe COVID-19. The cytokine storm associated with COVID-19 is thought to contribute to disease progression and is associated with poor outcomes in patients - as abivertinib inhibits the release of multiple cytokines at once, it may provide more pronounced clinical benefits as compared to agents targeting single pathways (e.g. interleukin-6 inhibitors). The study is expected to be completed in March 2021.
Abivertinib is an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, abivertinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR. |
| Molecular Formula |
C26H26FN7O2
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| Molecular Weight |
487.53
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| Exact Mass |
487.213
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| Elemental Analysis |
C, 64.05; H, 5.38; F, 3.90; N, 20.11; O, 6.56
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| CAS # |
1557267-42-1
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| Related CAS # |
Avitinib maleate;1557268-88-8
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| PubChem CID |
72734520
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.697
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
752
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=C(C=CC=1N1CCN(C)CC1)NC1N=C(C2C=CNC=2N=1)OC1C=CC=C(C=1)NC(C=C)=O
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| InChi Key |
UOFYSRZSLXWIQB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26FN7O2/c1-3-23(35)29-17-5-4-6-19(15-17)36-25-20-9-10-28-24(20)31-26(32-25)30-18-7-8-22(21(27)16-18)34-13-11-33(2)12-14-34/h3-10,15-16H,1,11-14H2,2H3,(H,29,35)(H2,28,30,31,32)
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| Chemical Name |
N-[3-[[2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide
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| Synonyms |
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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. |
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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) |
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 | 2.0512 mL | 10.2558 mL | 20.5116 mL | |
| 5 mM | 0.4102 mL | 2.0512 mL | 4.1023 mL | |
| 10 mM | 0.2051 mL | 1.0256 mL | 2.0512 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03856697 | Not yet recruiting | Drug: Placebo Gefitinib Tablets Drug: Gefitinib Tablets |
Advanced Non-small Cell Lung Cancer |
Hangzhou ACEA Pharmaceutical Research Co., Ltd. |
March 2019 | Phase 3 |
| NCT03574402 | Recruiting | Drug: Avitinib Maleate Drug: Afatinib |
Carcinoma, Non-Small-Cell Lung | Guangdong Association of Clinical Trials |
July 9, 2018 | Phase 2 |
| NCT04440007 | Completed | Drug: Abivertinib Other: Standard of Care |
Covid-19 | Sorrento Therapeutics, Inc. | October 9, 2020 | Phase 2 |
| NCT04528667 | Completed | Drug: STI-5656 Drug: Placebo |
Covid19 | Sorrento Therapeutics, Inc. | January 6, 2021 | Phase 2 |
| NCT03053219 | Completed | Drug: AC0010 | Carcinoma，Non-Small-Cell Lung | Hangzhou ACEA Pharmaceutical Research Co., Ltd. |
November 2016 | Phase 1 |
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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