IndraLab
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Ruxolitinib inhibits JAK1. 120 / 122
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"Ruxolitinib, which inhibits JAK2 but also TYK2, JAK1 and JAK3 XREF_BIBR at similar degrees demonstrated durable reduction in splenomegaly and constitutional symptoms with improved quality of life in comparison to placebo controlled XREF_BIBR or best available therapy XREF_BIBR in phase 3 trials and an impact on survival for patients originally randomized to ruxolitinib compared with those originally randomized to placebo in both COMFORT trials XREF_BIBR."
eidos
"6 , 7 , 8 , 9 Ruxolitinib blocks JAK1 , JAK2 , and STAT signaling pathways , suppresses immune responses , and has positive effects on interstitial pneumonia associated with idiopathic juvenile arthritis , bronchiolitis obliterans after HSCT , and COVID-19-related acute respiratory distress syndrome ."
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"Ruxolitinib inhibits JAK1 and JAK2 and thereby interferes with, respectively, the common cytokine receptor γ-chain (used by IL-2, IL-4, IL-7, IL-9, IL-15); the gp130 pathway (IL-6, IL-11, OSM, LIF); the class II cytokine receptor family (IFN-α/β, IFN-γ, IL-10) (JAK1); and the EPO, TPO, IFNγ, and βc family (IL-3, IL-5, GM-CSF) (JAK2)."
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"The use of JAK1 and JAK2 inhibitors such as ruxolitinib and baricitinib for GvHD prophylaxis may limit the need for expensive and labor-intensive ex vivo cellular manipulations 38 and may also reduce the use of broadly immunosuppressive agents that may themselves contribute to disease relapse, morbidity, and mortality after allo-HSCT."
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"Of these compounds they found that ruxolitinib and gogicide A (which are inhibitors of JAK1 and the Golgi specific brefeldin A resistant guanine nucleotide exchange factor GBF1, respectively) markedly decreased virus titers in human cells infected with influenza virus without affecting cell viability."
eidos
"To our knowledge , the accurate incidence of PCP and mycobacterial infection during ruxolitinib treatment has not been reported , but ruxolitinib suppresses the JAK1 / 2 signaling pathway , thereby affecting many cytokines and growth factors that are important for the immune function ."
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"This increase in responsiveness to pruritogens was mediated via neuronal Janus kinase (JAK)-1. The authors reported that inhibition of JAK-1 by ruxolitinib or deletion of neuronal JAK-signaling in mice significantly reduced scratching in a murine AD model even in the presence of skin inflammation."
eidos
"Moreover , other broad-spectrum cytokine inhibitors - - such as ruxolitinib , which blocks JAK1 and JAK2 , or itacitinib , which blocks JAK1 ( kinases that are required for cytokine receptor signalling ) - - would be expected to blunt the effects of pro-inflammatory cytokines such as IFNgamma and IL-6 ( refs37 ,105 ) ."
| PMC
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"Our previous study demonstrated that leptin promoted PLOD2 mediated breast cancer metastasis via the activation of PI3K and AKT and JAK and STAT3 signaling pathways, while ruxolitinib (a selective inhibitor of JAK1 and JAK2) and LY294002 (an inhibitor of PI3Ks) reversed leptin induced activation of these signals [XREF_BIBR]."
| PMC
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"For instance, ruxolitinib (a selective inhibitor of JAK1 and JAK2), crizotinib (a c-Met and ALK inhibitor) and AT7519 (an inhibitor of cyclin-dependent kinases) have been reported for treatment of myelofibrosis, non-small cell lung carcinoma and refractory solid tumors respectively (Nitulescu et al., 2015)."
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"Similarly, Ruxolitinib inhibits the influenza prey protein JAK1, a part of the Pathways in cancer gene-set.implications both in terms of improving baseline lung function and reducing the risk of adverse consequences after SARS-CoV2 exposure.Schematic representation of drug repositioning and precision implementation in lung function deficits directed by causal enrichment of environmental and genetic risk factors."
| DOI
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"It is conceivable that reduced drug availability or insufficient inhibition of IL7R signaling, as ruxolitinib mainly inhibits JAK1 and JAK2 while IL7R can also activate JAK3, are responsible for the inability of ruxolitinib to block the development of Ph ALL in vivo.Intriguingly, our experiments point to an unpredicted escape mechanism of transformed cells during TKI treatment."
eidos
"Rationale for the trial Since ruxolitinib suppresses the JAK1 / 2 dependent cytokine response , we hypothesized that ruxolitinib might attenuate the cytokine mediated inflammatory tissue damage in GvHD and thus might favorably affect the severity and course of GvHD after allo-HCT ."
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"By directly targeting both JAK1 and JAK2 through small-molecule inhibition, ruxolitinib elicits a reduction in splenomegaly and disease related symptoms in patients with intermediate- or high-risk myelofibrosis while maintaining an acceptable toxicity profile and a low treatment discontinuation rate."
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"Ruxolitinib, the first JAKinib approved by the United States Food and Drug Administration (FDA), is a potent inhibitor of JAK1 and JAK2, used for primary myelofibrosis and its effects have been also studied in MDS, AML, ALL, chronic myelomonocytic leukemia (CMML) and chronic myeloid leukemia (CML)."
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"Most experience has been in patients with myelofibrosis in phase I/II trials employing INCB018424 (a potent and selective inhibitor of JAK1 and JAK2), TG101348 (a structure based drug designed to inhibit JAK2 with great selectivity), CEP-701 (a multikinase inhibitor), and XL019 (a selective JAK2 inhibitor whose clinical development has been halted because of neurotoxicity)."
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"19 Like ruxolitinib, baracitinib (formerly designated INCB028050) is also a Jak1 and Jak2 inhibitor which showed efficacy in a highly active RA patient group resistant to disease modifying drugs and biologics with superior results in higher doses up to 4 or 8 mg once daily within 2 weeks with dose dependent side effects to include decrease of hemoglobin and neutrophil count and increase of LDL and creatinine with good overall tolerability."