IndraLab

Statements

Ruxolitinib inhibits STAT1. 14 / 14
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"Ruxolitinib only partially attenuated IFN-α induced loss of quiescence in Jak2 LT-HSCs (Fig. 7e), again demonstrating that LT-HSC pSTAT1 signaling was unable to be completely blocked by ruxolitinib."
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"There was an over 20-fold difference in the potency of ruxolitinib inhibition of STAT1 and STAT3 phosphorylation (IC 50 of 1.3 x10 -8 M), as compared with STAT5 phosphorylation (IC 50 of 2.8 x10 -7 M) (XREF_FIG)."
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"As shown in XREF_FIG, ruxolitinib decreased JAK1, JAK2, STAT1 and pSTAT1 (S727) protein levels in a dose dependent manner in LS411N and SW620 cells."
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"Ruxolitinib suppresses the hyperresponsiveness of STAT1 to ligand stimulation, leading to the normalization of Th1 and follicular T helper cell responses (112), and the partial rescue of NK cell differentiation and function (109)."
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"Ruxolitinib for two hours abrogated the interferon response of ACE2 and STAT1 (Fig. 6c) ."
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"1muM of Ruxolitinib (JAK1/2 inhibitor) and 5muM of Tofacitinib (JAK1/3 inhibitor) suppressed the IL-27-mediated STAT-1, -3 and -5 activation (XREF_SUPPLEMENTARY) without any significant change in cell viability (data not shown)."
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"Lastly, pretreatment of cells with ruxolitinib for two hours abrogated the interferon response of ACE2 and STAT1 (Fig. 6c)."
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"Finally, Ruxolitinib administration can limit STAT1 activation in patients carrying STAT1 gain of function mutations."
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"This mechanism may be relevant in CML, since it was shown that cells of IFNa-resistant patients lack STAT1 expression [17] and in PV, when STAT1 function is inhibited by ruxolitinib."
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"Mechanistically , ruxolitinib inhibited the secretion of IL-6 , TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro , indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway ."
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"To date, myelofibrosis treatment of two patients with Ruxolitinib, which inhibits JAK1,2 and likely STAT1, is hypothesized to have contributed to the development of cryptococcosis in these individuals [27, 28]."
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"JAK-STAT inhibitor Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL infiltration to induce a Tc1 and Th1 immune response in the tumor microenvironment in an orthotopic pancreatic cancer mouse model."
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"Interestingly ex vivo treatment with ruxolitinib was able to completely block STAT1, suggesting an inadequate intracellular drug concentration in LT-HSCs [172]."
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"Ruxolitinib may be predicted to block STAT1 activation through inhibition of JAK1."
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