| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
EGFR (IC50 = 0.75 nM); EGFRL858R (IC50 = 0.5 nM); EGFRT790M (IC50 = 0.79 nM); EGFRL858R/T790M (IC50 = 2.3 nM); ErbB2 (IC50 = 19 nM)
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|---|---|
| ln Vitro |
AV-412 has an IC50 of 43 nM for EGFR and 282 nM for ErbB2 to inhibit 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). With a double mutation of EGFR (L858R and T790M), the gefitinib-resistant H1975 cell line is mutated against EGFR. AV-412 reverses EGFR signal.
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| ln Vivo |
AV-412 (30 mg/kg) completely inhibits the tumor growth of the A431 and BT-474 cell lines, which overexpress EGFR and ErbB2, respectively, in animal studies using cancer xenograft models. EGFR and ErbB2 autophosphorylation is inhibited by AV-412 at a dose that is consistent with its antitumor efficacy. AV-412 exhibits significant effects when different dosing schedules are used; however, a once-weekly schedule does not show the same effects, indicating that frequent dosing is preferable for this compound. Additionally, on the ErbB2-overexpressing breast cancer KPL-4 cell line, which is resistant to gefitinib, AV-412 exhibits a strong antitumor effect[1].
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| Enzyme Assay |
Purified EGFR from A431 cell membranes and recombinant intracellular kinase domains of EGFR, EGFRL858R, EGFRT790M, and EGFRL858R/T790M are utilized. With the exception of EGFRT790M, which uses 250 µM of the GGMEDIYFEFMGGKKK peptide substrate, kinase reactions are conducted in 8 mM MOPS (pH 7.0), 0.2 mM ethylenediaminetetraacetic acid (EDTA), 10 mM MnCl2, 10 mM Mg acetate, 0.1 mg/mL poly(Glu, Tyr) 4:1, [γ33P-ATP], and 5–10 mU of enzyme. The addition of ATP starts the phosphorylation process, which lasts for 40 minutes at room temperature. After adding 3% phosphoric acid to halt the reaction, aliquots of the reaction mixture are spotted onto a filtermat. The filter is scintillation counted after being rinsed to get rid of any non-specifically bound peptides[1].
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| Cell Assay |
In order to investigate how AV-412 affects growth factor-dependent cell proliferation, A431 and A7r5 cells are cultivated for 24 hours at 37°C with 50 ng/mL platelet-derived growth factor and 1 ng/mL epidermal growth factor, respectively. Measurements are made of the 3H-thymidine incorporation during this time[1].
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| Animal Protocol |
Mice: In research investigating the relationship between the dosing regimen and TE-8 tumor efficacy, AV-412 is given once weekly, once daily, or once every other day for a period of two weeks. One day following the last treatment, the mice are killed, and the tumors are removed and weighed. Tumor-bearing mice are given a single injection of AV-412, and 4 hours later, the tumors are removed for analysis of tumor phosphorylation[1].
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| References |
| Molecular Formula |
C27H28CLFN6O
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|---|---|
| Molecular Weight |
507.0022
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| Exact Mass |
506.199
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| CAS # |
451492-95-8
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| Related CAS # |
AV-412;451493-31-5
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| PubChem CID |
9806229
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| Appearance |
White to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
672.9±55.0 °C at 760 mmHg
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| Flash Point |
360.7±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.663
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| LogP |
5.22
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
850
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZAJXXUDARPGGOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28ClFN6O/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)11-13-35/h5-7,14-17H,1,10-13H2,2-4H3,(H,33,36)(H,30,31,32)
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| Chemical Name |
N-[4-(3-chloro-4-fluoroanilino)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazolin-6-yl]prop-2-enamide
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| Synonyms |
AV-412
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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 |
| 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 (~33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9724 mL | 9.8619 mL | 19.7239 mL | |
| 5 mM | 0.3945 mL | 1.9724 mL | 3.9448 mL | |
| 10 mM | 0.1972 mL | 0.9862 mL | 1.9724 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 |
| NCT00551850 | Completed | Drug: AV-412 | Advanced Cancer Refractory Cancer |
AVEO Pharmaceuticals, Inc. | October 2007 | Phase 1 |
| NCT00381654 | Terminated | Drug: AV-412 | Tumor | AVEO Pharmaceuticals, Inc. | October 2006 | Phase 1 |
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