| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AV-412 Tosylate (also known as AV412; MP-412), the tosyulate salt of AV412, is a novel, 2nd generation and orally bioavailable EGFR inhibitor with IC50s of 0.75, 0.5, 0.79, 2.3, 19 nM for EGFR, EGFRL858R, EGFRT790M, EGFRL858R/T790M and ErbB2, respectively. It has potential antineoplastic activity. EGFR/HER2 inhibitor AV-412 binds to and inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to first-generation kinase inhibitors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization.
| 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].
|
|---|---|
| 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].
|
| 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
|
| Molecular Formula |
C41H44CLFN6O7S2
|
|---|---|
| Molecular Weight |
851.405460000001
|
| CAS # |
451493-31-5
|
| Related CAS # |
AV-412 free base;451492-95-8
|
| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)O.CC1=CC=C(C=C1)S(=O)(=O)O.CC(C)(C#CC1=CC2=C(C=C1NC(=O)C=C)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)N4CCN(CC4)C
|
| InChi Key |
GTWJVFFZCKODEV-UHFFFAOYSA-N
|
| 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)
|
| 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)
|
| Synonyms |
MP-412 AV412MP 412 AV 412MP412 AV-412 AV-412 tosylate
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 28 mg/mL (~32.89 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA