Avitinib

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

Avitinib (AC-0010, AC0010) 是一种口服、不可逆、突变选择性 EGFR 抑制剂，针对 EGFR L858R/T790M 的 IC50 为 0.18 nM。

Avitinib (AC-0010, AC0010) is an orally available, irreversible, and mutant-selective EGFR inhibitor with IC50 of 0.18 nM against EGFR L858R/T790M; displays 43-fold greater potency over wild-type EGFR (IC50=7.68 nM); selectively inhibits mutant EGFR phosphorylation (IC50 =7.3 nM and 2.8 nM) in NCI-H1975 and NIH/3T3_TC32T8 cells, 115- and 298-fold more sensitive than that of the inhibition of wild type EGFR in A431; overcomes T790M-induced resistance in animal models and lung cancer patients without hyperglycemia or other severe adverse effects.Lung Cancer Phase 2 Clinical(In Vitro):Avitinib is structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors such as osimertinib and rociletinib. Avitinib is designed specifically to inhibit EGFR active mutations and the T790M acquired resistant mutation, while sparing wild type EGFR. Avitinib selectively inhibits EGFR active and T790M mutations with up to 298-fold increase in potency compared to wild-type EGFR. Avitinib exhibits potent inhibitory activity with IC50 value of 0.18 nM against EGFR L858R/T790M double mutations, nearly 43-fold greater potency over wild-type EGFR (IC50=7.68 nM). Avitinib selectively inhibits mutant EGFR phosphorylation with IC50 values of 7.3 nM and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells, about 115- and 298-fold more sensitive than that of the inhibition of wild type EGFR in A431. (In Vivo):Oral administration of avitinib at daily dose of 500 mg/kg results in complete remission of tumors with EGFR active and T790M mutations for over 143 days with no weight loss. Three major metabolites of avitinib are tested and show no wild-type EGFR inhibition and off-target effects such as inhibition of IGF-1R. Avitinib is safe in non-small cell lung cancer (NSCLC) patients at the dose range between 50 mg and 550 mg once per day and no hyperglycemia and other severe adverse effects are detected such as grade 3 QT prolongation.

Western Blot AnalysisCell Line:NCI-H1975, HCC827, A431 cells.Concentration:0.13 nM, 0.64 nM, 3.2 nM, 16 nM, 80 nM, 0.4 μM, 2 μM Incubation Time:2 h Result:Selectively inhibits mutant EGFR phosphorylation with IC50 values of 7.3 and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells.

Animal Model:Nu/Nu nude mice (Six- to 8-week-old) injected with NCI-H1975 and A431 cells Dosage:12.5, 50, and 500 mg/kg Administration:Orally administration; once daily; for 14 days Result:Inhibited EGFR-mutant tumor growth but not wild-type EGFR tumor growth.

AC-0010 | AC0010

Angiogenesis

EGFR

EGFR

Cancer

Lung Cancer

1557267-42-1

487.539

C26H26FN7O2

>98% (HPLC)

DMSO: 88 mg/mL (180.5 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )

C=CC(NC1=CC=CC(OC2=C3C(NC=C3)=NC(NC4=CC=C(N5CCN(C)CC5)C(F)=C4)=N2)=C1)=O

N-[3-[[2-[[3-Fluoro-4-(4-methyl-1-piperazinyl)phenyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]-2-propenamide

(-20℃)

With Ice Pack

≥ 2 years