AV-412

中文名称:

AV-412

中文同义词:

N-[4-[(3-氯-4-氟苯基)氨基]-7-[3-甲基-3-(4-甲基-1-哌嗪基)-1-丁炔-1-基]-6-喹唑啉基]-2-丙烯酰胺;EGFR抑制剂(AV-412 FREE BASE);EGFR抑制剂(AV-412);N-(4-((3-氯-4-氟苯基)氨基)-7-(3-甲基-3-(4-甲基哌嗪-1-基)丁-1-炔-1-基)喹唑啉-6-基)丙烯酰胺

英文名称:

MP-412

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]-;AV-412 (free base);N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-yn-1-yl)quinazolin-6-yl)acrylamide;N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-yn-1-yl)quin;AV-412;MP-412;N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butyn-1-yl]-6-quinazolinyl]-2-propenamide;AV-412 free base (MP-412 free base)

CAS号:

451492-95-8

分子式:

C27H28ClFN6O

分子量:

507

EINECS号:

相关类别:

抑制剂;信号转导通路激酶抑制剂;细胞生物学试剂

Mol文件:

451492-95-8.mol

沸点 

672.9±55.0 °C(Predicted)

密度 

1.33

酸度系数(pKa)

11.61±0.43(Predicted)

生物活性

AV-412 free base (MP-412 free base) 是 EGFR 抑制剂，抑制EGFR，EGFRL858R，EGFRT790M，EGFRL858R/T790M 和 ErbB2的 IC50 值分别为0.75，0.5，0.79，2.3，19 nM。

靶点

EGFR 0.75 nM (IC 50 ) ErbB2 19 nM (IC 50 ) EGFR L858R 0.51 nM (IC 50 ) EGFR L858R/T790M 2.3 nM (IC 50 ) EGFR T790M 0.79 nM (IC 50 )

EGFR 0.75 nM (IC 50 )

ErbB2 19 nM (IC 50 )

体外研究

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.

体内研究

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.