451493-31-5
451493-31-5 結(jié)構(gòu)式
基本信息
MP412
AV-412 / MP-412
AV-412 Tosylate
451492-95-8 (AV-412 FREE BASE)
MP-412
AV412
AV 412
MP412
MP 412
N-[4-(3-Chloro-4-fluoroanilino)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazolin-6-yl]prop-2-enamide tosylate
N-[4-(3-chloro-4-fluoroanilino)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazolin-6-yl]prop-2-enamide,4-methylbenzenesulfonic acid
N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butynyl]-6-quinazolinyl]-2-propenamide bis(4-methylbenzenesulfonate)
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)
物理化學(xué)性質(zhì)
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)
常見問題列表
|
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.