AV 412
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 |
| 颜色 | 浅黄至黄绿色 |
AV 412 用途与合成方法
|
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.
