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  • 94
    Millipore azd 1480
    <t>AZD1480</t> inhibits tumor-associated integrin αvβ3 expression and MMP activity
    Azd 1480, supplied by Millipore, used in various techniques. Bioz Stars score: 94/100, based on 5 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/azd 1480/product/Millipore
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    95
    Selleck Chemicals azd 1480
    Mutations in the JAK2V617F kinase domain confer resistance to JAK2 tyrosine kinase inhibitors Growth of BaF3.EpoR cells expressing JAK2V617F (◆) and the additional Y931C (□), G935R (△)), R938L (×), I960V (○) or E985K (◊) mutations was determined in response to ruxolitinib (A) or CYT-387, TG101348, <t>AZD1480</t> and lestaurtinib (B) at various concentrations, as indicated (n=4). Changes in growth in response to JAK2 inhibitors were calculated relative to cells that were treated with the solvent DMSO.
    Azd 1480, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 95/100, based on 16 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    91
    Santa Cruz Biotechnology azd 1480
    Inhibition of Rac or JAK2 prevents STAT5 phosphorylation without influencing prolactin endocytosis. Eph4 cells were seeded onto plastic and LrBM added to the differentiation medium as appropriate. After 24 hours, cells were treated with inhibitors (JAK2 inhibitor <t>(AZD-1480,</t> 10 µM; ( A – C ) or Rac inhibitor (EHT 1864, 25–100 µM; D-E)) for 15 mins and then stimulated with Prl (3 μg/ml) as indicated for 15 mins before cells were acid washed to remove surface Prl and lysed. Samples were analysed by SDS-PAGE/western blotting with phospho-Y 694 STAT5, total STAT5a, Prl or tubulin specific antibodies, and quantification of relative STAT5 phosphorylation ( B , E ) and Prl internalisation ( C , F ) from Odyssey scanned fluorescent images performed using ImageJ. Yellow line indicates background signal in the absence of exogenous Prl. Western blots are representative of, and graphs show normalised data from, at least 3 independent experiments. *p
    Azd 1480, supplied by Santa Cruz Biotechnology, used in various techniques. Bioz Stars score: 91/100, based on 2 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/azd 1480/product/Santa Cruz Biotechnology
    Average 91 stars, based on 2 article reviews
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    90
    AstraZeneca azd 1480
    JAK inhibition reduces tumor burden and inflammation in Kras/Irs-1 −/− mice. ( A ) Representative H E-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor <t>(AZD-1480),</t> JAK-1 inhibitor
    Azd 1480, supplied by AstraZeneca, used in various techniques. Bioz Stars score: 90/100, based on 13 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/azd 1480/product/AstraZeneca
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    91
    Exelixis azd1480
    JAK inhibition reduces tumor burden and inflammation in Kras/Irs-1 −/− mice. ( A ) Representative H E-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor <t>(AZD-1480),</t> JAK-1 inhibitor
    Azd1480, supplied by Exelixis, used in various techniques. Bioz Stars score: 91/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/azd1480/product/Exelixis
    Average 91 stars, based on 3 article reviews
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    91
    Mimetics azd1480
    JAK inhibition reduces tumor burden and inflammation in Kras/Irs-1 −/− mice. ( A ) Representative H E-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor <t>(AZD-1480),</t> JAK-1 inhibitor
    Azd1480, supplied by Mimetics, used in various techniques. Bioz Stars score: 91/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    90
    Cell Signaling Technology Inc azd1480
    Low doses of JAK2 chemical inhibitors induce a paradoxical increase in MKs production both in vitro and in vivo. (A) The effect of <t>AZD1480,</t> a JAK2 chemical inhibitor, at different concentrations on cellular proliferation of CD34 + cells from cord blood cultured in MSS with TPO at 10 ng/mL. Cells were counted at D8. (B) CD34 + cells were cultured with TPO for 6 days. After a 12-hour cytokine starvation, these cells were restimulated with 10 ng/mL TPO with or without AZD1480 pretreatment, at 0.2 μM during 2 hours. We determined the efficacy of AZD1480 on cell signaling by immunoblotting. (C) CD34 + cells from cytapheresis were cultured in MSS with TPO, with or without AZD1480 at a concentration of 0.2 μM. Cellular proliferation was evaluated until D13 and CD41 and CD42 expression was determined by flow cytometry at D8 (D). (E) C57BL/6 mice were treated with different doses of ruxolitinib, a JAK2 inhibitor used in clinics (20 and 60 mg/kg of body weight per day) or vehicule (methocellulose 0.5%, tween 80 0.05%) by oral gavage, twice daily. Blood samples were analyzed after 5 days of treatment. (F) Platelet counts for C57BL/6 mice treated during 5 days with vehicule (n = 9), ruxolitinib at 20 mpk (n = 12), or 60 mpk (n = 9). Error bars represent mean ± standard deviation of 3 (A,F) or 2 (C) independent experiments. * P
    Azd1480, supplied by Cell Signaling Technology Inc, used in various techniques. Bioz Stars score: 90/100, based on 14 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 90 stars, based on 14 article reviews
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    85
    AstraZeneca jak2 inhibitor azd1480
    <t>AZD1480</t> induces paradoxical hyperphosphorylation of <t>JAK2,</t> TYK2 and MAP Kinases (ERK, p38) in HL cells. ( a ) Representative western blot assay of the three HL cell lines treated with increasing concentrations of AZD 1480 (0.1–5 μm for 72 h). Whole-cell lysates examined for p-JAK2 (two antibodies against Y1007/1008 at the activation loop obtained from different clones (see Materials and Methods)), JAK2, p-TYK2 Y1054/1055, TYK2, p-JAK3 Y980 and JAK3. ( b ) Representative western blot assay showing increased levels of ERK, p38 and SHP-2 phosphorylation in HD-LM2 and L-428, after treatment for 72 h with increasing doses of AZD1480 (0.1–5 μm). In contrast, L-540 showed a dose-dependent inhibition of ERK and p38 activation without increased SHP-2 phosphorylation. SOCS-3 levels decreased in all the cell lines. ( c ) After incubation with 1 μm AZD1480 for 72 h, cell culture supernatants were analyzed for IL-8, IP-10 and RANTES levels by enzyme-linked immunosorbent assay. In the bar graphs, each value is the mean of three independent experiments performed in triplicate. * P
    Jak2 Inhibitor Azd1480, supplied by AstraZeneca, used in various techniques. Bioz Stars score: 85/100, based on 12 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    91
    LC Laboratories jak inhibitor azd1480
    Effect of <t>AZD1480</t> on phosphorylation of STAT3 and production of IgA1 and galactose-deficient (Gd-IgA1) by IgA1-secreting cells stimulated with interleukin-6 (IL-6). IgA1-secreting cell lines derived from peripheral blood mononuclear cells of 3 healthy control subjects (HCs) and 3 IgA nephropathy (IgAN) patients were used. (a) Production of IgA1 and (b) Gd-IgA1 by IgA1-secreting cells from HCs and IgAN patients after IL-6 stimulation with and without AZD1480 pretreatment (0.1–2 μM). Mean values + SD from 1 representative experiment with 3 samples each are shown. (c) Effect of AZD1480 on phosphorylation of Y705 STAT3 induced by IL-6 in HC or IgAN cells. One of 3 similar blots is shown. (d) Densitometric analysis of data from (c).
    Jak Inhibitor Azd1480, supplied by LC Laboratories, used in various techniques. Bioz Stars score: 91/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    AZD1480 inhibits tumor-associated integrin αvβ3 expression and MMP activity

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: AZD1480 inhibits tumor-associated integrin αvβ3 expression and MMP activity

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Expressing, Activity Assay

    AZD1480-treatment inhibits ovarian tumor growth and ascites production in MISIIR-TAg mice

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: AZD1480-treatment inhibits ovarian tumor growth and ascites production in MISIIR-TAg mice

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Mouse Assay

    AZD1480-mediated tumor growth inhibition is accompanied by reduced STAT3 activation

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: AZD1480-mediated tumor growth inhibition is accompanied by reduced STAT3 activation

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Inhibition, Activation Assay

    Expression of STAT3 target genes is altered in AZD1480-treated ovarian tumors

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: Expression of STAT3 target genes is altered in AZD1480-treated ovarian tumors

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Expressing

    AZD1480-mediated JAK/STAT3 inhibition reduces T cell populations in the peritoneal tumor microenvironment

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: AZD1480-mediated JAK/STAT3 inhibition reduces T cell populations in the peritoneal tumor microenvironment

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Inhibition

    AZD1480 treatment reduces phosphorylated STAT3 levels and inhibits ovarian carcinoma cell migration and adhesion

    Journal: Molecular cancer therapeutics

    Article Title: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    doi: 10.1158/1535-7163.MCT-14-0800

    Figure Lengend Snippet: AZD1480 treatment reduces phosphorylated STAT3 levels and inhibits ovarian carcinoma cell migration and adhesion

    Article Snippet: For in vivo drug dosing, AZD1480 was formulated in 0.5% hypermellose/0.1%Tween 80 (Sigma).

    Techniques: Migration

    Mutations in the JAK2V617F kinase domain confer resistance to JAK2 tyrosine kinase inhibitors Growth of BaF3.EpoR cells expressing JAK2V617F (◆) and the additional Y931C (□), G935R (△)), R938L (×), I960V (○) or E985K (◊) mutations was determined in response to ruxolitinib (A) or CYT-387, TG101348, AZD1480 and lestaurtinib (B) at various concentrations, as indicated (n=4). Changes in growth in response to JAK2 inhibitors were calculated relative to cells that were treated with the solvent DMSO.

    Journal: Leukemia

    Article Title: Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms

    doi: 10.1038/leu.2011.255

    Figure Lengend Snippet: Mutations in the JAK2V617F kinase domain confer resistance to JAK2 tyrosine kinase inhibitors Growth of BaF3.EpoR cells expressing JAK2V617F (◆) and the additional Y931C (□), G935R (△)), R938L (×), I960V (○) or E985K (◊) mutations was determined in response to ruxolitinib (A) or CYT-387, TG101348, AZD1480 and lestaurtinib (B) at various concentrations, as indicated (n=4). Changes in growth in response to JAK2 inhibitors were calculated relative to cells that were treated with the solvent DMSO.

    Article Snippet: As expected, we did not observe any change in sensitivity of the M929I mutation towards CYT-387, TG101348, AZD1480 or lestaurtinib.

    Techniques: Expressing

    Macrophage-mediated proliferation of NBT2 cells is dependent on STAT3 phosphorylation (A) Mean fold change in percent of BrdU-positive NBT2 cells treated with solvent or JAK1/2 inhibitors AZD1480 (AZD) or ruxolitinib at indicated concentrations for NBT2 cells either alone or in co-culture with macrophages. Data were compiled from at least 3 independent experiments in triplicates; (B) Effects of AZD1480 and ruxolinitib on pSTAT3, STAT3, and MYC protein levels in lysates of NBT2 cells without or with a 6 and 24 hour co-culture with syngeneic macrophages in presence of AZD1480 (5 μM) or ruxolitinib (1 μM) as assessed by immunoblotting; (C) Immunoblot analysis of pSTAT3, STAT3, and MYC levels in protein lysates of three low MYC-expressing human NBL cell lines (LAN-6, CHLA-172, and CHLA-79) after 24 hour co-cultures with macrophages without or with ruxolitinib (1 μM); (D) Immunoblot analysis of STAT3 and pSTAT3 levels in protein lysates of tumors from NB-Tag mice or of subcutaneous tumors (Sub-Q) growing in NSG mice treated with ruxolitinib (60 mg/kg) by oral gavage twice daily for one week. (E) Tumor growth in NSG mice injected subcutaneously with 1X10 6 NBT2 tumor cells alone in one shoulder or co-injected in the opposite shoulder with equal number of macrophages that were conditioned for 24-36 hours with NBT2 cells in the transwell system. Animals were administered ruxolitinib (60 mg/kg) or drug vehicle by oral gavage twice daily for 3 weeks [ANOVA p

    Journal: Oncotarget

    Article Title: Tumor-associated macrophages promote neuroblastoma via STAT3 phosphorylation and up-regulation of c-MYC

    doi: 10.18632/oncotarget.21066

    Figure Lengend Snippet: Macrophage-mediated proliferation of NBT2 cells is dependent on STAT3 phosphorylation (A) Mean fold change in percent of BrdU-positive NBT2 cells treated with solvent or JAK1/2 inhibitors AZD1480 (AZD) or ruxolitinib at indicated concentrations for NBT2 cells either alone or in co-culture with macrophages. Data were compiled from at least 3 independent experiments in triplicates; (B) Effects of AZD1480 and ruxolinitib on pSTAT3, STAT3, and MYC protein levels in lysates of NBT2 cells without or with a 6 and 24 hour co-culture with syngeneic macrophages in presence of AZD1480 (5 μM) or ruxolitinib (1 μM) as assessed by immunoblotting; (C) Immunoblot analysis of pSTAT3, STAT3, and MYC levels in protein lysates of three low MYC-expressing human NBL cell lines (LAN-6, CHLA-172, and CHLA-79) after 24 hour co-cultures with macrophages without or with ruxolitinib (1 μM); (D) Immunoblot analysis of STAT3 and pSTAT3 levels in protein lysates of tumors from NB-Tag mice or of subcutaneous tumors (Sub-Q) growing in NSG mice treated with ruxolitinib (60 mg/kg) by oral gavage twice daily for one week. (E) Tumor growth in NSG mice injected subcutaneously with 1X10 6 NBT2 tumor cells alone in one shoulder or co-injected in the opposite shoulder with equal number of macrophages that were conditioned for 24-36 hours with NBT2 cells in the transwell system. Animals were administered ruxolitinib (60 mg/kg) or drug vehicle by oral gavage twice daily for 3 weeks [ANOVA p

    Article Snippet: STAT3 inhibition experiments NBT2 cells were cultured with and without macrophages in the presence of the STAT3 inhibitor AZD1480 or ruxolitinib (Selleckchem, Houston, TX).

    Techniques: Co-Culture Assay, Expressing, Mouse Assay, Injection

    Variability of endogenous protein abundance correlates with single cell response to chemical inhibition. (A) IL-2 stimulation of the JAK-STAT pathway. (B) Single cell pSTAT5 abundance in response to JAK inhibitor AZD1480. Inset, the coefficient of variation (CV) response to inhibition. (C) Single cell contour plot of total STAT5 abundance and pSTAT5 in cells not treated with inhibitor, [I jak ] = 0. Curve shows the resulting geometric mean of the pSTAT5 abundance conditioned on STAT5 abundance per cell. (D) Cell-to-Cell Variability Analysis reveals that the pSTAT5 response amplitude is correlated with STAT5 abundance. In addition, the sensitivity of cells to inhibition (IC 50 ) exhibits a small negative correlation with STAT5 abundance (errorbars are standard deviation of experimental duplicates).

    Journal: bioRxiv

    Article Title: Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis

    doi: 10.1101/038000

    Figure Lengend Snippet: Variability of endogenous protein abundance correlates with single cell response to chemical inhibition. (A) IL-2 stimulation of the JAK-STAT pathway. (B) Single cell pSTAT5 abundance in response to JAK inhibitor AZD1480. Inset, the coefficient of variation (CV) response to inhibition. (C) Single cell contour plot of total STAT5 abundance and pSTAT5 in cells not treated with inhibitor, [I jak ] = 0. Curve shows the resulting geometric mean of the pSTAT5 abundance conditioned on STAT5 abundance per cell. (D) Cell-to-Cell Variability Analysis reveals that the pSTAT5 response amplitude is correlated with STAT5 abundance. In addition, the sensitivity of cells to inhibition (IC 50 ) exhibits a small negative correlation with STAT5 abundance (errorbars are standard deviation of experimental duplicates).

    Article Snippet: The JAK inhibitor AZD1480 and SRC inhibitor Dasatinib were purchased from Selleckchem.

    Techniques: Inhibition, Standard Deviation

    CCVA reveals the most likely mechanism of AZD1480 in live single cells. (A) Model diagrams that represent three possible mechanisms of inhibition. (B) Each model was tested against our data by measuring the sum of squared residuals (Total Residuals) between our model predictions and the data points - a lower value means better agreement between model and data. The model was fit to all the data point presented in (C). (C) Overlay of data (circles) with the optimal model and parameter set from fit (lines). (D) A linear transform of the data was derived from the optimal model and the corresponding parameters reveal agreement between model (line) and the data (open circles), (See Eq. S8 in Supplementary Materials for details regarding the nonlinear transformation). (E) Overlay of measured IC 50 with respect to STAT5 abundance as measured from CCVA analysis of data (triangles; errorbars standard deviation experimental duplicates) and predicted by our optimal model (line).

    Journal: bioRxiv

    Article Title: Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis

    doi: 10.1101/038000

    Figure Lengend Snippet: CCVA reveals the most likely mechanism of AZD1480 in live single cells. (A) Model diagrams that represent three possible mechanisms of inhibition. (B) Each model was tested against our data by measuring the sum of squared residuals (Total Residuals) between our model predictions and the data points - a lower value means better agreement between model and data. The model was fit to all the data point presented in (C). (C) Overlay of data (circles) with the optimal model and parameter set from fit (lines). (D) A linear transform of the data was derived from the optimal model and the corresponding parameters reveal agreement between model (line) and the data (open circles), (See Eq. S8 in Supplementary Materials for details regarding the nonlinear transformation). (E) Overlay of measured IC 50 with respect to STAT5 abundance as measured from CCVA analysis of data (triangles; errorbars standard deviation experimental duplicates) and predicted by our optimal model (line).

    Article Snippet: The JAK inhibitor AZD1480 and SRC inhibitor Dasatinib were purchased from Selleckchem.

    Techniques: Inhibition, Derivative Assay, Transformation Assay, Standard Deviation

    Inhibition of JAK2/STAT5 signaling pathway blocked the promotive effect of Pro-Gly on IGF-1 expression and secretion in the HepG2 cells. (A) Western blot analysis of phospho-JAK2 (p-JAK2), JAK2, phospho-STAT5 (p-STAT5), STAT5 and prepro IGF-1 in HepG2 cells after 6 h or 24 h incubation in the presence of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM), respectively. β-actin was used as loading control. The panels shown are the representative bands of 3 independent experiments with 6 replicates. (B) Mean ± SEM of immunoblotting bands of prepro IGF-1, p-JAK2/JAK2 and p-STAT5/STAT5 ( n = 6). The intensities of the bands were expressed as the arbitrary units. (C) IGF-1 mRNA level in HepG2 cells after 24 h incubation in the presence of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM) ( n = 6). GAPDH was used as housekeeping gene. (D) Effects of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM) on IGF-1 levels in the supernatant of HepG2 cells ( n = 6). Bars that do not share the same letter are significantly different ( P

    Journal: Frontiers in Endocrinology

    Article Title: The Dipeptide Pro-Gly Promotes IGF-1 Expression and Secretion in HepG2 and Female Mice via PepT1-JAK2/STAT5 Pathway

    doi: 10.3389/fendo.2018.00424

    Figure Lengend Snippet: Inhibition of JAK2/STAT5 signaling pathway blocked the promotive effect of Pro-Gly on IGF-1 expression and secretion in the HepG2 cells. (A) Western blot analysis of phospho-JAK2 (p-JAK2), JAK2, phospho-STAT5 (p-STAT5), STAT5 and prepro IGF-1 in HepG2 cells after 6 h or 24 h incubation in the presence of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM), respectively. β-actin was used as loading control. The panels shown are the representative bands of 3 independent experiments with 6 replicates. (B) Mean ± SEM of immunoblotting bands of prepro IGF-1, p-JAK2/JAK2 and p-STAT5/STAT5 ( n = 6). The intensities of the bands were expressed as the arbitrary units. (C) IGF-1 mRNA level in HepG2 cells after 24 h incubation in the presence of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM) ( n = 6). GAPDH was used as housekeeping gene. (D) Effects of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM) on IGF-1 levels in the supernatant of HepG2 cells ( n = 6). Bars that do not share the same letter are significantly different ( P

    Article Snippet: JAK2 inhibitor AZD1480 (S2162) were purchased from Selleck (Shanghai, China), Dulbecco's modified Eagle's medium (DMEM), HepatoZYME-SFM and fetal bovine serum (FBS) were purchased from Gibco BRL (Carlsbad, CA).

    Techniques: Inhibition, Expressing, Western Blot, Incubation

    Injection of JAK2/STAT5 inhibitor abolished the promotive effect of Pro-Gly on IGF-1 expression and secretion in mice. Twenty-eight 6-week old female mice were randomly divided into 4 groups ( n = 7). (A) Western blot analysis of phospho-JAK2 (p-JAK2), JAK2, phospho-STAT5 (p-STAT5), STAT5 and prepro IGF-1 in mice liver after injection. β-actin was used as loading control. The mice were intraperitoneal injected with physiological saline (Control), Pro-Gly (100 mg/kg, 1 h), JAK2 inhibitor AZD1480 (30 mg/kg, 3 h) or Pro-Gly+AZD1480 in a volume of 100 μL, respectively. (B) Mean ± SEM of immunoblotting bands of prepro IGF-1, p-JAK2/JAK2, and p-STAT5/STAT5 ( n = 7). The intensities of the bands were expressed as the arbitrary units. (C) IGF-1 mRNA level in mice liver ( n = 7). (D) Serum levels of IGF-1 ( n = 7). Bars that do not share the same letter are significantly different ( P

    Journal: Frontiers in Endocrinology

    Article Title: The Dipeptide Pro-Gly Promotes IGF-1 Expression and Secretion in HepG2 and Female Mice via PepT1-JAK2/STAT5 Pathway

    doi: 10.3389/fendo.2018.00424

    Figure Lengend Snippet: Injection of JAK2/STAT5 inhibitor abolished the promotive effect of Pro-Gly on IGF-1 expression and secretion in mice. Twenty-eight 6-week old female mice were randomly divided into 4 groups ( n = 7). (A) Western blot analysis of phospho-JAK2 (p-JAK2), JAK2, phospho-STAT5 (p-STAT5), STAT5 and prepro IGF-1 in mice liver after injection. β-actin was used as loading control. The mice were intraperitoneal injected with physiological saline (Control), Pro-Gly (100 mg/kg, 1 h), JAK2 inhibitor AZD1480 (30 mg/kg, 3 h) or Pro-Gly+AZD1480 in a volume of 100 μL, respectively. (B) Mean ± SEM of immunoblotting bands of prepro IGF-1, p-JAK2/JAK2, and p-STAT5/STAT5 ( n = 7). The intensities of the bands were expressed as the arbitrary units. (C) IGF-1 mRNA level in mice liver ( n = 7). (D) Serum levels of IGF-1 ( n = 7). Bars that do not share the same letter are significantly different ( P

    Article Snippet: JAK2 inhibitor AZD1480 (S2162) were purchased from Selleck (Shanghai, China), Dulbecco's modified Eagle's medium (DMEM), HepatoZYME-SFM and fetal bovine serum (FBS) were purchased from Gibco BRL (Carlsbad, CA).

    Techniques: Injection, Expressing, Mouse Assay, Western Blot

    IFNγ-induced JAK2/STAT1/IRF-1/PD-L1 signaling is inhibited with AZD1480 (an ATP-competitive JAK2 inhibitor) and fludarabine (a STAT1 inhibitor depleting STAT1 mRNA and protein) in EBV (+) GC cells. ( A ) EBV (+) SNU-719 cells were incubated with increasing concentrations of AZD1480 or fludarabine (5, 10, and 20 μM) for 2 h, and then transfected with the PD-L1 promoter luciferase vector. After 4 h, cells were stimulated with 10 ng/mL IFNγ for 24 h, luciferase activities were measured. ( B ) EBV (+) SNU-719 cells were treated with 5 μM of AZD1480 or fludarabine for 2 h, followed by stimulation with 10 ng/mL IFNγ for 24 h. The mRNA levels of JAK2, STAT1, IRF-1, and PD-L1 were determined by qRT-PCR. ( C , D ) After treatments with AZD1480 or fludarabine under the same conditions as ( B ), the protein levels of STAT1, IRF-1, and PD-L1 proteins were determined by immunoblotting and quantified relative to β-actin. The data are presented as mean ± SEM (n = 3). *P

    Journal: Scientific Reports

    Article Title: IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma

    doi: 10.1038/s41598-017-18132-0

    Figure Lengend Snippet: IFNγ-induced JAK2/STAT1/IRF-1/PD-L1 signaling is inhibited with AZD1480 (an ATP-competitive JAK2 inhibitor) and fludarabine (a STAT1 inhibitor depleting STAT1 mRNA and protein) in EBV (+) GC cells. ( A ) EBV (+) SNU-719 cells were incubated with increasing concentrations of AZD1480 or fludarabine (5, 10, and 20 μM) for 2 h, and then transfected with the PD-L1 promoter luciferase vector. After 4 h, cells were stimulated with 10 ng/mL IFNγ for 24 h, luciferase activities were measured. ( B ) EBV (+) SNU-719 cells were treated with 5 μM of AZD1480 or fludarabine for 2 h, followed by stimulation with 10 ng/mL IFNγ for 24 h. The mRNA levels of JAK2, STAT1, IRF-1, and PD-L1 were determined by qRT-PCR. ( C , D ) After treatments with AZD1480 or fludarabine under the same conditions as ( B ), the protein levels of STAT1, IRF-1, and PD-L1 proteins were determined by immunoblotting and quantified relative to β-actin. The data are presented as mean ± SEM (n = 3). *P

    Article Snippet: Treatment with JAK2 and STAT1 inhibitors AZD1480 and fludarabine were purchased from selleckchem (Houston, TX, USA).

    Techniques: Incubation, Transfection, Luciferase, Plasmid Preparation, Quantitative RT-PCR

    EPO augmented M2 polarization via Jak2/STAT3/STAT6 pathway. ( a ) RAW 264.7 cells were subjected to 20 ng/ml IL-4 in the presence or absence of EPO (50 IU/ml) for 24 h. Protein expressions of related molecules were measured and representative photographs are exhibited. ( b ) To further confirm the contribution of Jak2/STAT3, RAW 264.7 cells stimulated by IL-4 and EPO were incubated with AZD1480 (an inhibitor of p-Jak2, 5 μ M) or Stattic (an inhibitor of p-STAT3, 10 μ M). Protein expressions of related molecules were measured and representative images are demonstrated. ( c ) Proposed pathways by which EPO promotes M2 polarization in the presence of IL-4. Experiments were performed in triplicate. Error bars represent S.D. * P

    Journal: Cell Death & Disease

    Article Title: Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization

    doi: 10.1038/cddis.2017.104

    Figure Lengend Snippet: EPO augmented M2 polarization via Jak2/STAT3/STAT6 pathway. ( a ) RAW 264.7 cells were subjected to 20 ng/ml IL-4 in the presence or absence of EPO (50 IU/ml) for 24 h. Protein expressions of related molecules were measured and representative photographs are exhibited. ( b ) To further confirm the contribution of Jak2/STAT3, RAW 264.7 cells stimulated by IL-4 and EPO were incubated with AZD1480 (an inhibitor of p-Jak2, 5 μ M) or Stattic (an inhibitor of p-STAT3, 10 μ M). Protein expressions of related molecules were measured and representative images are demonstrated. ( c ) Proposed pathways by which EPO promotes M2 polarization in the presence of IL-4. Experiments were performed in triplicate. Error bars represent S.D. * P

    Article Snippet: We further determined the contribution of Jak2/STAT3 to EPO-induced M2 polarization by applying p-Jak2 inhibitor AZD1480 (Selleck) and p-STAT3 inhibitor Stattic (Selleck).

    Techniques: Incubation

    Constitutive STAT3 phosphorylation on stiff matrices is dependent on ROCK and JAK2. Normal human lung fibroblasts were incubated with the indicated concentrations of ROCK inhibitor Y27632 or myosin II inhibitor Blebbistatin (A), JAK2 inhibitor AZD1408, JAK1/2 inhibitor Ruxolitinib or JAK3 inhibitor Tofacitinib (B), FAK inhibitor PF562271 or TGF-β type I receptor inhibitor SB431542 (C) for 1 h and STAT3 phosphorylation (Y705) was assessed by ELISA and normalized to total protein (* P

    Journal: Journal of Cell Science

    Article Title: RNAi screening identifies a mechanosensitive ROCK-JAK2-STAT3 network central to myofibroblast activation

    doi: 10.1242/jcs.209932

    Figure Lengend Snippet: Constitutive STAT3 phosphorylation on stiff matrices is dependent on ROCK and JAK2. Normal human lung fibroblasts were incubated with the indicated concentrations of ROCK inhibitor Y27632 or myosin II inhibitor Blebbistatin (A), JAK2 inhibitor AZD1408, JAK1/2 inhibitor Ruxolitinib or JAK3 inhibitor Tofacitinib (B), FAK inhibitor PF562271 or TGF-β type I receptor inhibitor SB431542 (C) for 1 h and STAT3 phosphorylation (Y705) was assessed by ELISA and normalized to total protein (* P

    Article Snippet: To test roles in STAT3 phosphorylation, inhibitors of ROCK (Y27632, 3-30 µM, STEMCELL Technologies), myosin II (Blebbistatin 3-30 µM, Selleckchem), JAK1 (Ruxolitinib, 1-10 µM, Selleckchem), JAK2 (AZD1480, 1-10 µM, Selleckchem), JAK3 (Tofacitinib, 1-10 µM, Selleckchem), TGF-β type I receptor (1-10 µM, Selleckchem) and FAK (PF562271, 1-10 µM, Selleckchem) were added to the cells and incubated for 1 h prior to lysis and measurement of STAT3 phosphorylation.

    Techniques: Incubation, Enzyme-linked Immunosorbent Assay

    Berberin inhibits CRC cell migration and invasion through COX-2/PGE 2 -JAK2/STAT3 mediated signaling pathway. A. and B. Extracts from SW620 cells treated with AZD1480 for 2 h, transfected with COX-2 over-expression construct for 24 h, treated with berberin (40 μM) for 48 h, were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin. C. and D. Extracts from SW620 cells treated with AZD1480 for 2 h, treated with berberin (40 μM) or PGE 2 (5 μM) for 48 h, were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin.

    Journal: PLoS ONE

    Article Title: Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

    doi: 10.1371/journal.pone.0123478

    Figure Lengend Snippet: Berberin inhibits CRC cell migration and invasion through COX-2/PGE 2 -JAK2/STAT3 mediated signaling pathway. A. and B. Extracts from SW620 cells treated with AZD1480 for 2 h, transfected with COX-2 over-expression construct for 24 h, treated with berberin (40 μM) for 48 h, were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin. C. and D. Extracts from SW620 cells treated with AZD1480 for 2 h, treated with berberin (40 μM) or PGE 2 (5 μM) for 48 h, were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin.

    Article Snippet: In comparison, using a JAK2 inhibitor (AZD1480), we similarly abrogated the pJAK2 and pSTAT3, resulting in the dampened cellular migration/invasion levels of CRC cells ( ).

    Techniques: Migration, Transfection, Over Expression, Construct

    Berberin blocks JAK2/STAT3 signaling in CRC cells. A. Extracts from SW620 and LoVo cells treated with berberin at indicated concentrations for 48 h were analyzed for pJAK2, JAK2, pSTAT3, STAT3 and beta-actin (as loading control). B. JAK inhibitor AZD1480 blocks JAK2/STAT3 signaling. Extracts from SW620 and LoVo cells treated with AZD1480 (5 μM) were analyzed for the expression of pJAK2, JAK2, pSTAT3, STAT3 and beta-actin. C. AZD1480 inhibits migration and invasion of CRC cells. The results shown are representative of three independent experiments. The bars and error bars represent the means ± SE, and the P -value was calculated using an independent t -test. ** P

    Journal: PLoS ONE

    Article Title: Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

    doi: 10.1371/journal.pone.0123478

    Figure Lengend Snippet: Berberin blocks JAK2/STAT3 signaling in CRC cells. A. Extracts from SW620 and LoVo cells treated with berberin at indicated concentrations for 48 h were analyzed for pJAK2, JAK2, pSTAT3, STAT3 and beta-actin (as loading control). B. JAK inhibitor AZD1480 blocks JAK2/STAT3 signaling. Extracts from SW620 and LoVo cells treated with AZD1480 (5 μM) were analyzed for the expression of pJAK2, JAK2, pSTAT3, STAT3 and beta-actin. C. AZD1480 inhibits migration and invasion of CRC cells. The results shown are representative of three independent experiments. The bars and error bars represent the means ± SE, and the P -value was calculated using an independent t -test. ** P

    Article Snippet: In comparison, using a JAK2 inhibitor (AZD1480), we similarly abrogated the pJAK2 and pSTAT3, resulting in the dampened cellular migration/invasion levels of CRC cells ( ).

    Techniques: Expressing, Migration

    A hypothetical illustration for the role of berberin. PGE2, the main catalyzed product of COX-2 from arachidonic acid, could bind to the EP receptor on the cell membrane, thereby activating the JAK2, followed by the phorphorylating of STAT3 in the Tyr705 site. The activated p-STAT3 forms the homo-or heterodimers, which translocate into the nucleus, bind to the downstream target gene MMP-2, MMP-9, and accelerate the tumor progression. Inhibiting the COX-2/PGE2 mediated JAK2/STAT3 signaling pathway, could be one of the mechanisms of the inhibitory effect of berberin on the invasion and metastasis in colorectal cancer.

    Journal: PLoS ONE

    Article Title: Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

    doi: 10.1371/journal.pone.0123478

    Figure Lengend Snippet: A hypothetical illustration for the role of berberin. PGE2, the main catalyzed product of COX-2 from arachidonic acid, could bind to the EP receptor on the cell membrane, thereby activating the JAK2, followed by the phorphorylating of STAT3 in the Tyr705 site. The activated p-STAT3 forms the homo-or heterodimers, which translocate into the nucleus, bind to the downstream target gene MMP-2, MMP-9, and accelerate the tumor progression. Inhibiting the COX-2/PGE2 mediated JAK2/STAT3 signaling pathway, could be one of the mechanisms of the inhibitory effect of berberin on the invasion and metastasis in colorectal cancer.

    Article Snippet: In comparison, using a JAK2 inhibitor (AZD1480), we similarly abrogated the pJAK2 and pSTAT3, resulting in the dampened cellular migration/invasion levels of CRC cells ( ).

    Techniques:

    COX-2/PGE 2 regulates JAK2/STAT3 signaling in CRC cells. A. and B. Extracts from SW620 and LoVo cells transfected with COX-2 over-expression or shRNA construct were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin. C. and D. Extracts from SW620 and LoVo cells treated with PGE 2 for indicated durations were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin.

    Journal: PLoS ONE

    Article Title: Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

    doi: 10.1371/journal.pone.0123478

    Figure Lengend Snippet: COX-2/PGE 2 regulates JAK2/STAT3 signaling in CRC cells. A. and B. Extracts from SW620 and LoVo cells transfected with COX-2 over-expression or shRNA construct were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin. C. and D. Extracts from SW620 and LoVo cells treated with PGE 2 for indicated durations were analyzed for pJAK2, JAK2, pSTAT3, STAT3, MMP-2, MMP-9 and beta-actin.

    Article Snippet: In comparison, using a JAK2 inhibitor (AZD1480), we similarly abrogated the pJAK2 and pSTAT3, resulting in the dampened cellular migration/invasion levels of CRC cells ( ).

    Techniques: Transfection, Over Expression, shRNA, Construct

    Inhibition of Rac or JAK2 prevents STAT5 phosphorylation without influencing prolactin endocytosis. Eph4 cells were seeded onto plastic and LrBM added to the differentiation medium as appropriate. After 24 hours, cells were treated with inhibitors (JAK2 inhibitor (AZD-1480, 10 µM; ( A – C ) or Rac inhibitor (EHT 1864, 25–100 µM; D-E)) for 15 mins and then stimulated with Prl (3 μg/ml) as indicated for 15 mins before cells were acid washed to remove surface Prl and lysed. Samples were analysed by SDS-PAGE/western blotting with phospho-Y 694 STAT5, total STAT5a, Prl or tubulin specific antibodies, and quantification of relative STAT5 phosphorylation ( B , E ) and Prl internalisation ( C , F ) from Odyssey scanned fluorescent images performed using ImageJ. Yellow line indicates background signal in the absence of exogenous Prl. Western blots are representative of, and graphs show normalised data from, at least 3 independent experiments. *p

    Journal: Scientific Reports

    Article Title: Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells

    doi: 10.1038/s41598-017-04783-6

    Figure Lengend Snippet: Inhibition of Rac or JAK2 prevents STAT5 phosphorylation without influencing prolactin endocytosis. Eph4 cells were seeded onto plastic and LrBM added to the differentiation medium as appropriate. After 24 hours, cells were treated with inhibitors (JAK2 inhibitor (AZD-1480, 10 µM; ( A – C ) or Rac inhibitor (EHT 1864, 25–100 µM; D-E)) for 15 mins and then stimulated with Prl (3 μg/ml) as indicated for 15 mins before cells were acid washed to remove surface Prl and lysed. Samples were analysed by SDS-PAGE/western blotting with phospho-Y 694 STAT5, total STAT5a, Prl or tubulin specific antibodies, and quantification of relative STAT5 phosphorylation ( B , E ) and Prl internalisation ( C , F ) from Odyssey scanned fluorescent images performed using ImageJ. Yellow line indicates background signal in the absence of exogenous Prl. Western blots are representative of, and graphs show normalised data from, at least 3 independent experiments. *p

    Article Snippet: EpH4 cells were treated with inhibitors (Pitstop-2 [15 µM, Abcam]; Dyngo-4a [60 µM, Abcam]; Filipin III [8 µM, Sigma-Aldrich]; AZD-1480 [10 µM, Santa Cruz Biotechnology]; EHT 1864 [25–100 µM, Tocris]) or an equal volume of DMSO (where appropriate) diluted in differentiation medium for 15 minutes at 37 °C before addition of Prl.

    Techniques: Inhibition, SDS Page, Western Blot

    A subset of ER stress-induced JAK1-dependent signaling is insensitive to kinase inhibition of JAK1. (A) Astrocytes were pretreated with JAK1/2 kinase inhibitor AZD1480 (1 μM) for 1 h before 0.5 h treatment with oncostatin M (OSM). Protein lysates were collected and analyzed by immunoblot. (B) Astrocytes were pretreated with AZD1480 for 1 h and then treated with thaps for 4 h. Gene expression was analyzed by RT-qPCR. Data are represented as means ± standard deviation. N = 3. ∗ p

    Journal: Frontiers in Cellular Neuroscience

    Article Title: Janus Kinase 1 Is Required for Transcriptional Reprograming of Murine Astrocytes in Response to Endoplasmic Reticulum Stress

    doi: 10.3389/fncel.2019.00446

    Figure Lengend Snippet: A subset of ER stress-induced JAK1-dependent signaling is insensitive to kinase inhibition of JAK1. (A) Astrocytes were pretreated with JAK1/2 kinase inhibitor AZD1480 (1 μM) for 1 h before 0.5 h treatment with oncostatin M (OSM). Protein lysates were collected and analyzed by immunoblot. (B) Astrocytes were pretreated with AZD1480 for 1 h and then treated with thaps for 4 h. Gene expression was analyzed by RT-qPCR. Data are represented as means ± standard deviation. N = 3. ∗ p

    Article Snippet: Thapsigargin and tunicamycin used were from EMD Millipore and AZD1480 was supplied from Santa Cruz Biotechnology.

    Techniques: Inhibition, Expressing, Quantitative RT-PCR, Standard Deviation

    JAK inhibition reduces tumor burden and inflammation in Kras/Irs-1 −/− mice. ( A ) Representative H E-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor (AZD-1480), JAK-1 inhibitor

    Journal: Proceedings of the National Academy of Sciences of the United States of America

    Article Title: Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma

    doi: 10.1073/pnas.1601989113

    Figure Lengend Snippet: JAK inhibition reduces tumor burden and inflammation in Kras/Irs-1 −/− mice. ( A ) Representative H E-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor (AZD-1480), JAK-1 inhibitor

    Article Snippet: We thank AstraZeneca for supplying AZD-1480 and AZ-289.

    Techniques: Inhibition, Mouse Assay, Staining

    No change in CC3 with JAK inhibition. ( A ) Representative images for CC3-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor (AZD-1480), JAK-1 inhibitor (AZ-289), or vehicle control. ( B ) Quantification

    Journal: Proceedings of the National Academy of Sciences of the United States of America

    Article Title: Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma

    doi: 10.1073/pnas.1601989113

    Figure Lengend Snippet: No change in CC3 with JAK inhibition. ( A ) Representative images for CC3-stained sections from Kras/Irs-1 +/+ and Kras/Irs-1 −/− mice treated with JAK-1/2 inhibitor (AZD-1480), JAK-1 inhibitor (AZ-289), or vehicle control. ( B ) Quantification

    Article Snippet: We thank AstraZeneca for supplying AZD-1480 and AZ-289.

    Techniques: Inhibition, Staining, Mouse Assay

    The JAK1/2 Inhibitor AZD1480 Suppresses Development of Atypical EAE

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: The JAK1/2 Inhibitor AZD1480 Suppresses Development of Atypical EAE

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques:

    Effect of AZD1480 on Th1- and Th17-induced Adoptive Transfer EAE

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: Effect of AZD1480 on Th1- and Th17-induced Adoptive Transfer EAE

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques: Adoptive Transfer Assay

    The JAK1/2 Inhibitor AZD1480 Has Direct Effects on Myeloid APCs and Th1 Cells

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: The JAK1/2 Inhibitor AZD1480 Has Direct Effects on Myeloid APCs and Th1 Cells

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques:

    AZD1480 Blocks JAK/STAT Activation and Gene Expression in Macrophages and DCs

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: AZD1480 Blocks JAK/STAT Activation and Gene Expression in Macrophages and DCs

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques: Activation Assay, Expressing

    Effect of AZD1480 on CD4+ T-cell Proliferation and Hematologic Parameters

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: Effect of AZD1480 on CD4+ T-cell Proliferation and Hematologic Parameters

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques:

    The JAK1/2 Inhibitor AZD1480 Suppresses Classical EAE

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: The JAK1/2 Inhibitor AZD1480 Suppresses Classical EAE

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques:

    AZD1480 Inhibits Activation of the JAK/STAT Pathway and Gene Expression in Human T-cells and Monocytes

    Journal: Journal of immunology (Baltimore, Md. : 1950)

    Article Title: Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of EAE

    doi: 10.4049/jimmunol.1301513

    Figure Lengend Snippet: AZD1480 Inhibits Activation of the JAK/STAT Pathway and Gene Expression in Human T-cells and Monocytes

    Article Snippet: AZD1480 , a JAK1/JAK2 inhibitor, was synthesized and provided by AstraZeneca R & D (Waltham, Massachusetts), and re-suspended in DMSO, as previously described ( , ).

    Techniques: Activation Assay, Expressing

    Low doses of JAK2 chemical inhibitors induce a paradoxical increase in MKs production both in vitro and in vivo. (A) The effect of AZD1480, a JAK2 chemical inhibitor, at different concentrations on cellular proliferation of CD34 + cells from cord blood cultured in MSS with TPO at 10 ng/mL. Cells were counted at D8. (B) CD34 + cells were cultured with TPO for 6 days. After a 12-hour cytokine starvation, these cells were restimulated with 10 ng/mL TPO with or without AZD1480 pretreatment, at 0.2 μM during 2 hours. We determined the efficacy of AZD1480 on cell signaling by immunoblotting. (C) CD34 + cells from cytapheresis were cultured in MSS with TPO, with or without AZD1480 at a concentration of 0.2 μM. Cellular proliferation was evaluated until D13 and CD41 and CD42 expression was determined by flow cytometry at D8 (D). (E) C57BL/6 mice were treated with different doses of ruxolitinib, a JAK2 inhibitor used in clinics (20 and 60 mg/kg of body weight per day) or vehicule (methocellulose 0.5%, tween 80 0.05%) by oral gavage, twice daily. Blood samples were analyzed after 5 days of treatment. (F) Platelet counts for C57BL/6 mice treated during 5 days with vehicule (n = 9), ruxolitinib at 20 mpk (n = 12), or 60 mpk (n = 9). Error bars represent mean ± standard deviation of 3 (A,F) or 2 (C) independent experiments. * P

    Journal: Blood

    Article Title: JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation

    doi: 10.1182/blood-2014-03-559815

    Figure Lengend Snippet: Low doses of JAK2 chemical inhibitors induce a paradoxical increase in MKs production both in vitro and in vivo. (A) The effect of AZD1480, a JAK2 chemical inhibitor, at different concentrations on cellular proliferation of CD34 + cells from cord blood cultured in MSS with TPO at 10 ng/mL. Cells were counted at D8. (B) CD34 + cells were cultured with TPO for 6 days. After a 12-hour cytokine starvation, these cells were restimulated with 10 ng/mL TPO with or without AZD1480 pretreatment, at 0.2 μM during 2 hours. We determined the efficacy of AZD1480 on cell signaling by immunoblotting. (C) CD34 + cells from cytapheresis were cultured in MSS with TPO, with or without AZD1480 at a concentration of 0.2 μM. Cellular proliferation was evaluated until D13 and CD41 and CD42 expression was determined by flow cytometry at D8 (D). (E) C57BL/6 mice were treated with different doses of ruxolitinib, a JAK2 inhibitor used in clinics (20 and 60 mg/kg of body weight per day) or vehicule (methocellulose 0.5%, tween 80 0.05%) by oral gavage, twice daily. Blood samples were analyzed after 5 days of treatment. (F) Platelet counts for C57BL/6 mice treated during 5 days with vehicule (n = 9), ruxolitinib at 20 mpk (n = 12), or 60 mpk (n = 9). Error bars represent mean ± standard deviation of 3 (A,F) or 2 (C) independent experiments. * P

    Article Snippet: Higher concentrations of AZD1480 (eg, 1 µM) completely inhibited cell proliferation and differentiation ( ).

    Techniques: In Vitro, In Vivo, Cell Culture, Concentration Assay, Expressing, Flow Cytometry, Cytometry, Mouse Assay, Standard Deviation

    AZD1480 induces paradoxical hyperphosphorylation of JAK2, TYK2 and MAP Kinases (ERK, p38) in HL cells. ( a ) Representative western blot assay of the three HL cell lines treated with increasing concentrations of AZD 1480 (0.1–5 μm for 72 h). Whole-cell lysates examined for p-JAK2 (two antibodies against Y1007/1008 at the activation loop obtained from different clones (see Materials and Methods)), JAK2, p-TYK2 Y1054/1055, TYK2, p-JAK3 Y980 and JAK3. ( b ) Representative western blot assay showing increased levels of ERK, p38 and SHP-2 phosphorylation in HD-LM2 and L-428, after treatment for 72 h with increasing doses of AZD1480 (0.1–5 μm). In contrast, L-540 showed a dose-dependent inhibition of ERK and p38 activation without increased SHP-2 phosphorylation. SOCS-3 levels decreased in all the cell lines. ( c ) After incubation with 1 μm AZD1480 for 72 h, cell culture supernatants were analyzed for IL-8, IP-10 and RANTES levels by enzyme-linked immunosorbent assay. In the bar graphs, each value is the mean of three independent experiments performed in triplicate. * P

    Journal: Blood Cancer Journal

    Article Title: The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma

    doi: 10.1038/bcj.2011.46

    Figure Lengend Snippet: AZD1480 induces paradoxical hyperphosphorylation of JAK2, TYK2 and MAP Kinases (ERK, p38) in HL cells. ( a ) Representative western blot assay of the three HL cell lines treated with increasing concentrations of AZD 1480 (0.1–5 μm for 72 h). Whole-cell lysates examined for p-JAK2 (two antibodies against Y1007/1008 at the activation loop obtained from different clones (see Materials and Methods)), JAK2, p-TYK2 Y1054/1055, TYK2, p-JAK3 Y980 and JAK3. ( b ) Representative western blot assay showing increased levels of ERK, p38 and SHP-2 phosphorylation in HD-LM2 and L-428, after treatment for 72 h with increasing doses of AZD1480 (0.1–5 μm). In contrast, L-540 showed a dose-dependent inhibition of ERK and p38 activation without increased SHP-2 phosphorylation. SOCS-3 levels decreased in all the cell lines. ( c ) After incubation with 1 μm AZD1480 for 72 h, cell culture supernatants were analyzed for IL-8, IP-10 and RANTES levels by enzyme-linked immunosorbent assay. In the bar graphs, each value is the mean of three independent experiments performed in triplicate. * P

    Article Snippet: Reagents and antibodies The JAK2 inhibitor AZD1480 was obtained from AstraZeneca, Inc. (Waltham, MA, USA).

    Techniques: Western Blot, Activation Assay, Clone Assay, Inhibition, Incubation, Cell Culture, Enzyme-linked Immunosorbent Assay

    Effect of AZD1480 on phosphorylation of STAT3 and production of IgA1 and galactose-deficient (Gd-IgA1) by IgA1-secreting cells stimulated with interleukin-6 (IL-6). IgA1-secreting cell lines derived from peripheral blood mononuclear cells of 3 healthy control subjects (HCs) and 3 IgA nephropathy (IgAN) patients were used. (a) Production of IgA1 and (b) Gd-IgA1 by IgA1-secreting cells from HCs and IgAN patients after IL-6 stimulation with and without AZD1480 pretreatment (0.1–2 μM). Mean values + SD from 1 representative experiment with 3 samples each are shown. (c) Effect of AZD1480 on phosphorylation of Y705 STAT3 induced by IL-6 in HC or IgAN cells. One of 3 similar blots is shown. (d) Densitometric analysis of data from (c).

    Journal: Kidney International Reports

    Article Title: Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

    doi: 10.1016/j.ekir.2017.07.002

    Figure Lengend Snippet: Effect of AZD1480 on phosphorylation of STAT3 and production of IgA1 and galactose-deficient (Gd-IgA1) by IgA1-secreting cells stimulated with interleukin-6 (IL-6). IgA1-secreting cell lines derived from peripheral blood mononuclear cells of 3 healthy control subjects (HCs) and 3 IgA nephropathy (IgAN) patients were used. (a) Production of IgA1 and (b) Gd-IgA1 by IgA1-secreting cells from HCs and IgAN patients after IL-6 stimulation with and without AZD1480 pretreatment (0.1–2 μM). Mean values + SD from 1 representative experiment with 3 samples each are shown. (c) Effect of AZD1480 on phosphorylation of Y705 STAT3 induced by IL-6 in HC or IgAN cells. One of 3 similar blots is shown. (d) Densitometric analysis of data from (c).

    Article Snippet: To determine the long-term effects of IL-6 treatment on phosphorylation of STAT3, EBV-immortalized, IgA1-producing cell lines derived from cells in the peripheral blood of IgAN patients (IgAN-PB cells) and HC (HC-PB cells) were exposed to IL-6 at a final concentration of 40 ng/ml for 1, 3, and 48 hours in the presence or absence of JAK inhibitor AZD1480 (0.3- or 2-μM concentration).

    Techniques: Derivative Assay

    Kinomic profiling of IgA1-secreting cells from healthy control subjects (HC) and IgA nephropathy (IgAN) patients stimulated with interleukin-6 (IL-6) with or without the AZD1480 inhibitor. Direct interaction mapping using GeneGo MetaCore of phosphopeptides that were significantly inhibited by AZD1480-treated lysate from IgA1-secreting cells derived from peripheral blood mononuclear cells from patients with IgAN but not those from HCs, after IL-6 stimulation. In addition, a Build a Network modeling tool was used to generate likely interactions that link uploaded objects (significant phosphopeptides inhibited in the cell lysate from IgAN patients) similar to the known pathway models. Pathways representing vascular endothelial growth factor receptor (VEGFR) and STAT signaling axes were found and are displayed as the networks Signal transduction VEGF, STAT3 signaling (red circles).

    Journal: Kidney International Reports

    Article Title: Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

    doi: 10.1016/j.ekir.2017.07.002

    Figure Lengend Snippet: Kinomic profiling of IgA1-secreting cells from healthy control subjects (HC) and IgA nephropathy (IgAN) patients stimulated with interleukin-6 (IL-6) with or without the AZD1480 inhibitor. Direct interaction mapping using GeneGo MetaCore of phosphopeptides that were significantly inhibited by AZD1480-treated lysate from IgA1-secreting cells derived from peripheral blood mononuclear cells from patients with IgAN but not those from HCs, after IL-6 stimulation. In addition, a Build a Network modeling tool was used to generate likely interactions that link uploaded objects (significant phosphopeptides inhibited in the cell lysate from IgAN patients) similar to the known pathway models. Pathways representing vascular endothelial growth factor receptor (VEGFR) and STAT signaling axes were found and are displayed as the networks Signal transduction VEGF, STAT3 signaling (red circles).

    Article Snippet: To determine the long-term effects of IL-6 treatment on phosphorylation of STAT3, EBV-immortalized, IgA1-producing cell lines derived from cells in the peripheral blood of IgAN patients (IgAN-PB cells) and HC (HC-PB cells) were exposed to IL-6 at a final concentration of 40 ng/ml for 1, 3, and 48 hours in the presence or absence of JAK inhibitor AZD1480 (0.3- or 2-μM concentration).

    Techniques: Derivative Assay, Transduction

    STAT3 activation by interleukin-6 (IL-6) was reduced by AZD1480 pretreatment. IgA1-secreting cell lines derived from peripheral blood mononuclear cells of 3 healthy control subjects (HCs) and 3 IgA nephropathy (IgAN) patients were used. (a) STAT3 Y705 phosphorylation was assessed 1, 3, and 48 hours after IL-6 stimulation with or without AZD1480 (0.3 or 2 μM). One of 3 similar blots is shown. (b) Densitometric analysis of data from (a).

    Journal: Kidney International Reports

    Article Title: Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

    doi: 10.1016/j.ekir.2017.07.002

    Figure Lengend Snippet: STAT3 activation by interleukin-6 (IL-6) was reduced by AZD1480 pretreatment. IgA1-secreting cell lines derived from peripheral blood mononuclear cells of 3 healthy control subjects (HCs) and 3 IgA nephropathy (IgAN) patients were used. (a) STAT3 Y705 phosphorylation was assessed 1, 3, and 48 hours after IL-6 stimulation with or without AZD1480 (0.3 or 2 μM). One of 3 similar blots is shown. (b) Densitometric analysis of data from (a).

    Article Snippet: To determine the long-term effects of IL-6 treatment on phosphorylation of STAT3, EBV-immortalized, IgA1-producing cell lines derived from cells in the peripheral blood of IgAN patients (IgAN-PB cells) and HC (HC-PB cells) were exposed to IL-6 at a final concentration of 40 ng/ml for 1, 3, and 48 hours in the presence or absence of JAK inhibitor AZD1480 (0.3- or 2-μM concentration).

    Techniques: Activation Assay, Derivative Assay