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HKI-272-來(lái)那替尼 Neratinib_JAK/STAT 信號(hào)通路-MedChemExpress LLC

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放大字體  縮小字體    發(fā)布日期:2019-09-02  來(lái)源:儀器信息網(wǎng)  作者:Mr liao  瀏覽次數(shù):641
核心提示:更新時(shí)間:2019-06-24 11:08:0134 聯(lián)系我們時(shí)請(qǐng)說(shuō)明是91化工儀器網(wǎng)上看到的信息,謝謝! 產(chǎn)品簡(jiǎn)介 品牌 MedChemExpress (MCE) 貨號(hào) HY-32721 規(guī)格 10 mM * 1 mL;5 mg;10 mg 供貨周期 現(xiàn)貨 應(yīng)用領(lǐng)域 生物產(chǎn)業(yè) Neratinib 是一種可口服的,不可逆的 tyrosine kinase 抑制劑,能夠抑制 HER2 和 EGFR 的活性,IC50 值分別為 59 nM 和 92 nM。 詳細(xì)介紹 Neratinib產(chǎn)品活性:Ner

聯(lián)系我們時(shí)請(qǐng)說(shuō)明是91化工儀器網(wǎng)上看到的信息,謝謝!


產(chǎn)品簡(jiǎn)介 品牌 MedChemExpress (MCE) 貨號(hào) HY-32721 規(guī)格 10 mM * 1 mL;5 mg;10 mg 供貨周期 現(xiàn)貨 應(yīng)用領(lǐng)域 生物產(chǎn)業(yè)     Neratinib 是一種可口服的,不可逆的 tyrosine kinase 抑制劑,能夠抑制 HER2 和 EGFR 的活性,IC50 值分別為 59 nM 和 92 nM。
詳細(xì)介紹 Neratinib

產(chǎn)品活性:Neratinib 是一種可口服的,不可逆的 tyrosine kinase 抑制劑,能夠抑制 HER2 和 EGFR 的活性,IC50 值分別為 59 nM 和 92 nM。

研究領(lǐng)域:JAK/STAT Signaling | Protein Tyrosine Kinase/RTK

作用靶點(diǎn):EGFR

In Vitro: Neratinib has inhibition of tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. Neratinib displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met. Neratinib selectively inhibits the proliferation of 3T3 cells transfected with the HER2 (3T3/neu), as well as two other HER-2-overexpressing SK-Br-3 and BT474 cells with IC50 values of 2-3 nM, displaying > 230-fold potency compared with non-transfected 3T3 cells as well as MDA-MB-435 and SW620 which are EGFR- and HER2-negative. Neratinib also inhibits the proliferation of EGFR-dependent A431 cells with an IC50 of 81 nM. Neratinib reduces HER2 receptor autophosphorylation in BT474 cells with an IC50 of 5 nM, and EGF-dependent phosphorylation of EGFR in A431 cells with IC50 of 3 nM. Blocking of HER-2 by Neratinib results in inhibition of downstream MAPK and Akt pathways with IC50 of 2 nM, more potently than Trastuzumab. Neratinib inhibits the cyclin D1 expression and the phosphorylation of the Rb-susceptibility gene production in BT474 cells with IC50 of 9 nM, leading to G1-S arrest and ultimately decreased cell proliferation.

In Vivo: Orally treated neratinib significantly inhibits the growth of 3T3/neu xenografts, with inhibition of 34%, 53%, 98%, and 98% at dose of 10, 20, 40, and 80 mg/kg/day, respectively. Consistent with the inhibition of HER-2 phosphorylation by 84% within 1 hour of administration at 40 mg/kg/day, Neratinib inhibits the growth of BT474 xenografts by 70-82%, 67%, and 93% at dose of 5, 10, and 40 mg/kg/day, respectively. Neratinib is also effective against SK-OV-3 xenografts with inhibition of 31% and 85% at 5 and 60 mg/kg/day, respectively. Neratinib is less potent against EGFR-dependent A431 xenografts than HER-2-dependent tumors, with 32% and 44% inhibition at 5 and 20 mg/kg/day, respectively. Neratinib displays little activity against MCF-7 and MX-1 xenografts expressing low levels of HER-2 and EGFR, with only 28% inhibition at 80 mg/kg/day, suggesting that Neratinib has selective activity for cells expressing HER-2 or EGFR.

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