AV 412
| 中文名称 | AV 412 |
|---|---|
| 中文同义词 | 化合物AV-412;MP-412; MP 412; MP412; AV-412; AV 412; AV412 |
| 英文名称 | 2-PropenaMide, N-[4-[(3-chloro-4-fluorophenyl)aMino]-7-[3-Methyl-3-(4-Methyl-1-piperazinyl)-1-butyn-1-yl]-6-quinazolinyl]-, 4-Methylbenzenesulfonate (1:2) |
| 英文同义词 | 2-PropenaMide, N-[4-[(3-chloro-4-fluorophenyl)aMino]-7-[3-Methyl-3-(4-Methyl-1-piperazinyl)-1-butyn-1-yl]-6-quinazolinyl]-, 4-Methylbenzenesulfonate (1:2);AV-412 / MP-412;N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butynyl]-6-quinazolinyl]-2-propenamide bis(4-methylbenzenesulfonate);AV-412 Tosylate;MP-412;MP412;451492-95-8 (AV-412 FREE BASE);N-[4-(3-Chloro-4-fluoroanilino)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazolin-6-yl]prop-2-enamide tosylate;MP-412;AV412;AV 412;MP412;MP 412 |
| CAS号 | 451493-31-5 |
| 分子式 | C41H44ClFN6O7S2 |
| 分子量 | 851.4054632 |
| EINECS号 | |
| 相关类别 | |
| Mol文件 | 451493-31-5.mol |
| 结构式 |  |
AV 412 性质
| 储存条件 | Store at -20°C |
|---|---|
| 溶解度 | DMSO:21.5(最大浓度 mg/mL);25.29(最大浓度 mM) DMSO:PBS (pH 7.2) (1:3):0.25(最大浓度 mg/mL);0.29(最大浓度. mM) DMF:15.0(最大浓度 mg/mL);17.64(最大浓度 mM) 乙醇:0.25(最大浓度 mg/mL);0.29(最大浓度 mM) |
| 形态 | 粉末 |
|
EGFR 0.75 nM (IC 50 ) |
EGFR L858R 0.5 nM (IC 50 ) |
EGFR T790M 0.79 nM (IC 50 ) |
EGFR L858R/T790M 2.3 nM (IC 50 ) |
ErbB2 19 nM (IC 50 ) |
AV-412 inhibits autophosphorylation of EGFR and ErbB2 with IC 50 of 43 and 282 nM, respectively. AV-412 also inhibits epidermal growth factor (EGF)-dependent cell proliferation with an IC 50 of 100 nM. AV-412 abrogates EGFR signaling in the gefitinib-resistant H1975 cell line, which harbors a double mutation of L858R and T790M in EGFR.
In animal studies using cancer xenograft models, AV-412 (30 mg/kg) demonstrates complete inhibition of tumor growth of the A431 and BT-474 cell lines, which overexpress EGFR and ErbB2, respectively. AV-412 suppresses autophosphorylation of EGFR and ErbB2 at the dose corresponding to its antitumor efficacy. When various dosing schedules are applied, AV-412 shows significant effects with daily and every-other-day schedules, but not with a once-weekly schedule, suggesting that frequent dosing is preferable for this compound. Furthermore, AV-412 shows a significant antitumor effect on the ErbB2-overexpressing breast cancer KPL-4 cell line, which is resistant to gefitinib.