AV 412

CAS号:451493-31-5
英文名: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)
中文名:AV 412
CBNumber:CB02626693
分子式:C41H44ClFN6O7S2
分子量:851.4054632
MOL File:451493-31-5.mol

AV 412化学性质

储存条件 :Store at -20°C
溶解度 :DMSO:21.5(Max Conc. mg/mL);25.29(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.29(Max Conc. mM)
DMF:15.0(Max Conc. mg/mL);17.64(Max Conc. mM)
Ethanol:0.25(Max Conc. mg/mL);0.29(Max Conc. mM)
形态 :Powder
颜色 :Light yellow to green yellow

AV 412性质、用途与生产工艺

生物活性 AV-412 (MP412) 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 )

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 )

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.

AV 412上下游产品信息

上游原料

下游产品

AV 412生产厂家