AV-412

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AV-412 是一种 EGFR 抑制剂（EGFR、EGFR T790M、EGFR L858R、EGFR L858R/T790M 和 ErbB2，IC50 为 0.75、0.79、0.5、2.3、19 nM）。在细胞中，MP-412 抑制 EGFR 和 ErbB2 的自身磷酸化IC(50) 分别为 43 和 282 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.(In Vitro):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 Vivo):n 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 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.

MP412

Angiogenesis

EGFR

EGFR|EGFR(L858R)|EGFR(T790M)|EGFR(L858R/T790M)|ErbB2

Cancer

Tumor

451493-31-5

851.41

C41H44ClFN6O7S2

>98% (HPLC)

DMSO:25 mg/mL (29.36 mM)

Cc1ccc(cc1)S(O)(=O)=O.Cc1ccc(cc1)S(O)(=O)=O.CN1CCN(CC1)C(C)(C)C#Cc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)C=C

——

(-20℃)

With Ice Pack

≥ 2 years