AV-412 是一种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 和 19 nM。

AV-412 is an EGFR inhibitor (EGFR, EGFR T790M, EGFR L858R, EGFR L858R/T790M and ErbB2 with IC50s of 0.75, 0.79, 0.5, 2.3, 19 nM).

In cells, MP-412 inhibited autophosphorylation of EGFR and ErbB2 with IC(50) of 43 and 282 nM, respectively.?It also inhibited epidermal growth factor (EGF)-dependent cell proliferation with an IC(50) of 100 nM.?Moreover, MP-412 abrogated 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, MP-412 (30 mg/kg) demonstrated complete inhibition of tumor growth of the A431 and BT-474 cell lines, which overexpress EGFR and ErbB2, respectively.?MP-412 suppressed autophosphorylation of EGFR and ErbB2 at the dose corresponding to its antitumor efficacy.?When various dosing schedules were applied, MP-412 showed 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, MP-412 showed a significant antitumor effect on the ErbB2-overexpressing breast cancer KPL-4 cell line, which is resistant to gefitinib.?These studies indicate that MP-412 has potential as a therapeutic agent for the treatment of cancers expressing EGFR and ErbB2, especially those resistant to the first generation of small-molecule inhibitors.

451493-31-5

C41H44ClFN6O7S2

851.41

MP412

DMSO:25 mg/mL (29.36 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years