| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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Purity: ≥98%
| Targets |
AV-412 Tosylate targets EGFR and HER2 (ErbB2). It is a dual kinase inhibitor that binds to both receptors. By inhibiting EGFR and HER2 signaling, it blocks the signaling pathways mediated by these receptors, which are involved in cancer cell growth and proliferation. This may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors.
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| ln Vitro |
AV-412 has an IC50 of 43 nM for EGFR and 282 nM for ErbB2 to prevent the autophosphorylation of these proteins. With an IC50 of 100 nM, AV-412 also suppresses the proliferation of cells that is dependent on epidermal growth factor (EGF). In the gefitinib-resistant H1975 cell line, which carries the EGFR double mutations L858R and T790M, AV-412 disrupts EGFR signaling [1].
In vitro, AV-412 (10 and 30 μM) induces ubiquitination and degradation of HER2 in SK-BR-3 cells. It decreases levels of HER2 and estrogen receptor α (ERα) and increases levels of Hsp70 in MCF-7 cells when used at a concentration of 10 μM. It completely inhibits the tumor growth of both H1650 and H1975 xenografts in nude mice. |
| ln Vivo |
AV-412 (30 mg/kg) showed full suppression of tumor growth in A431 and BT-474 cell lines overexpressing EGFR and ErbB2, respectively, in animal tests employing cancer xenograft models. EGFR and ErbB2 autophosphorylation is inhibited by AV-412 at dosages that are consistent with its anticancer efficaciousness. AV-412 demonstrated substantial effects when varied dosing regimens were applied, but not in the weekly regimens. This suggests that frequent dosing is not advantageous for this chemical. is favored. Furthermore, on the ErbB2-overexpressing breast cancer KPL-4 cell line, which is resistant to gefitinib, AV-412 demonstrated strong anti-tumor activities [1].
In vivo, AV-412 completely inhibits the tumor growth of both H1650 and H1975 xenografts in nude mice. It suppresses tumor growth via the inhibition of EGFR. AV-412 shows dose-dependent inhibition of both large and small lung tumors in two mature animal models. Its mechanism of action holds promise for benefiting patients with non-small cell lung cancer, metastatic breast cancer, pancreatic cancer, head and neck cancer, and hormone-resistant prostate cancer. |
| Enzyme Assay |
The enzymatic activity of AV-412 can be assessed using kinase assays with recombinant EGFR and HER2 kinases. The kinases are incubated with their substrates and ATP in the presence of varying concentrations of AV-412. The extent of phosphorylation is measured using techniques such as radioactive labeling or immunoassay. The IC₅₀ values for EGFR and HER2 inhibition are determined from dose-response curves.
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| Cell Assay |
To evaluate the cellular effects of AV-412, cancer cell lines expressing EGFR and/or HER2 (e.g., SK-BR-3, MCF-7, H1650, H1975) are treated with the compound. Cell proliferation, viability, and apoptosis are assessed using standard assays. The inhibition of EGFR and HER2 phosphorylation is confirmed by Western blotting using phospho-specific antibodies. The effects on downstream signaling pathways (e.g., MAPK, PI3K/AKT) are also evaluated.
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| Animal Protocol |
In vivo studies with AV-412 typically involve administration to tumor-bearing mice in xenograft models. The compound's effects on tumor growth, angiogenesis, and survival are assessed. Pharmacokinetic parameters, such as bioavailability and half-life, are also characterized. The compound's effects on HER2 and ERα levels in tumors can be assessed by immunohistochemistry.
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| ADME/Pharmacokinetics |
AV-412 Tosylate has a molecular formula and weight that are not specified in the available literature. Its CAS number is 451493-31-5. It is a dual EGFR/ErbB2 kinase inhibitor. It is soluble in DMSO and other organic solvents. The purity is typically >98%. It should be stored according to the manufacturer's instructions.
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| Toxicity/Toxicokinetics |
Specific toxicology data for AV-412 Tosylate are not extensively detailed in the available literature. However, it has been studied in clinical trials, indicating a degree of safety. As with all research compounds, standard safety precautions should be taken when handling AV-412 Tosylate. It is intended for research use only and is not for human consumption.
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| References |
[1]. Suzuki T, et al. Pharmacological characterization of MP-412 (AV-412), a dual epidermal growth factor receptorand ErbB2 tyrosine kinase inhibitor. Cancer Sci. 2007 Dec;98(12):1977-84
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| Additional Infomation |
AV-412, an EGFR/HER2 inhibitor, is a second-generation, orally bioavailable dual-kinase inhibitor with potential antitumor activity. AV-412 binds to and inhibits epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), thereby inhibiting tumor growth and angiogenesis and causing regression of EGFR/HER2-expressing tumors. This drug may be effective against EGFR/HER2-expressing tumor cells resistant to first-generation kinase inhibitors. EGFR and HER2 are receptor tyrosine kinases that play important roles in tumor cell proliferation and tumor angiogenesis.
Drug Indications Studied for the treatment of cancer/tumors (not specified). Mechanism of Action AV-412 effectively inhibits EGFR L858R mutations and has demonstrated dose-dependent inhibition of both large and small lung tumors in two mature animal models, achieving complete regression of lung tumors at doses ineffective with erlotinib. The mechanism of action of AV-412 holds promise for benefiting patients with non-small cell lung cancer, metastatic breast cancer, pancreatic cancer, head and neck cancer, and hormone-resistant prostate cancer. AV-412 Tosylate (MP-412) is a dual EGFR/ErbB2 kinase inhibitor. It binds to and inhibits EGFR and HER2, leading to inhibition of tumor growth and angiogenesis. AV-412 has shown efficacy in preclinical models of non-small cell lung cancer, breast cancer, and other EGFR/HER2-expressing tumors. It is a research tool for studying EGFR/HER2 signaling and developing targeted cancer therapies. |
| Molecular Formula |
C41H44CLFN6O7S2
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|---|---|
| Molecular Weight |
851.405460000001
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| Exact Mass |
850.239
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| CAS # |
451493-31-5
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| Related CAS # |
AV-412 free base;451492-95-8
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| PubChem CID |
11700696
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
9.334
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
58
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(C1=CC=C(C)C=C1)(O)=O.C=CC(NC2=CC3=C(NC4=CC=C(F)C(Cl)=C4)N=CN=C3C=C2C#CC(N5CCN(C)CC5)(C)C)=O.O=S(C6=CC=C(C)C=C6)(O)=O
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| InChi Key |
GTWJVFFZCKODEV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28ClFN6O.2C7H8O3S/c1-5-25(36)33-23-16-20-24(30-17-31-26(20)32-19-6-7-22(29)21(28)15-19)14-18(23)8-9-27(2,3)35-12-10-34(4)11-13-352*1-6-2-4-7(5-3-6)11(8,9)10/h5-7,14-17H,1,10-13H2,2-4H3,(H,33,36)(H,30,31,32)2*2-5H,1H3,(H,8,9,10)
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| Chemical Name |
N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-yn-1-yl)quinazolin-6-yl)acrylamide
bis(4-methylbenzenesulfonate)
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| Synonyms |
MP-412 AV412MP 412 AV 412MP412 AV-412 AV-412 tosylate
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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. |
| 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 : ≥ 28 mg/mL (~32.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.44 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 (2.44 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1745 mL | 5.8726 mL | 11.7452 mL | |
| 5 mM | 0.2349 mL | 1.1745 mL | 2.3490 mL | |
| 10 mM | 0.1175 mL | 0.5873 mL | 1.1745 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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