AV-412(MP-412)是EGFR和ErbB2的双重抑制剂，能抑制突变型EGFR（L858R和T790M，IC₅₀分别为0.51 nM和0.79 nM），还能抑制EGFR和ErbB2的自磷酸化，IC₅₀分别为43和282 nM。

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

MP-412 free base

light-yellow solid

DMSO : 50 mg/mL (98.62 mM; Need ultrasonic)

EGFR

AV-412 inhibits autophosphorylation of EGFR and ErbB2 with IC50 of 43 and 282 nM, respectively. AV-412 also inhibits epidermal growth factor (EGF)-dependent cell proliferation with an IC50 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.