| In vitro |
E6201 is distinguished as an inhibitor explicitly targeting the MEKK1 and MEK families, without impacting the MAPK family members, demonstrating selective inhibitory effects on MEKK1-induced phosphorylation of MEK1, MKK4, and MKK6 (IC50 values: 31, 522, and 65 nM, respectively). Notably, at a concentration of 10 μM, E6201 does not influence other proteins in the MAPK family such as ERK2, JNKs, and p38 MAPK. Its capability extends to thwarting LPS-induced TNF transcription (IC50: 50±14 nM) while barely affecting β-actin transcription up to concentrations of 3 μM. E6201 also shows inhibitory actions on specific receptor tyrosine kinases—including VEGFR2, PDGFR, the hepatocyte growth factor receptor, and EGFR (IC50 values: 350, 860, 1100, and 5400 nM, respectively)—and the nonreceptor tyrosine kinase Syk (IC50: 460 nM), while sparing ZAP-70, IKK, and PKC activity even at elevated concentrations of 10 μM and 100 μM, respectively. This compound further inhibits IL-2 production post-PHA-P activation (IC50: 18 nM), curtails proliferation of EGF-stimulated human keratinocytes (IC50: 160 nM), and suppresses IL-8 production in keratinocytes post-IL-1α or TNFα stimulation (IC50 values: 60 and 30 nM, respectively). Additionally, E6201 effectively inhibits production of TNFα, IL-1, IL-6, and IL-8 in human PBMCs (IC50 values: 20, 16, 52, and 53 nM, respectively), showcases potent inhibition of triple-negative breast cancer (TNBC) cell proliferation and colony formation in a dose-dependent manner, induces G1 phase cell cycle arrest, and triggers apoptosis in TNBC cells at 1 μM, substantiated by a significant reduction in phospho-ERK expression levels and sustained effects observed through Western Blot Analysis.
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投与量変換
