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Gsk2795039

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GSK2795039 is a small molecule compound that functions as a selective inhibitor of the Janus Kinase (JAK) enzyme family. It exhibits inhibitory activity against JAK1, JAK2, JAK3, and TYK2 kinases. The core function of GSK2795039 is to modulate the JAK-STAT signaling pathway by inhibiting the catalytic activity of the targeted JAK enzymes.

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Lab products found in correlation

N acetyl cysteine (nac), by Merck Group (1 mentions) G 6976, by Cell Signaling Technology (1 mentions) Cellrox, by Thermo Fisher Scientific (1 mentions) Bv421, by BD (1 mentions) L 012, by Merck Group (1 mentions) Mitosox, by Thermo Fisher Scientific (1 mentions) Sytox green, by Thermo Fisher Scientific (1 mentions) Hoechst 33342, by Merck Group (1 mentions) Myxothiazol, by Merck Group (1 mentions) Idebenone, by Cayman Chemical (1 mentions) Zileuton, by Cayman Chemical (1 mentions) Oligomycin, by Merck Group (1 mentions) Pd146176, by Cayman Chemical (1 mentions) Gkt137831, by Cayman Chemical (1 mentions) Piericidin a, by Cayman Chemical (1 mentions) 2 thenoyltrifluoroacetone ttfa, by Merck Group (1 mentions) Antimycin a, by Merck Group (1 mentions) Rotenone, by Merck Group (1 mentions) N acetyl l cysteine, by Abcam (1 mentions) Nitazoxanide, by Selleck Chemicals (1 mentions)

9 protocols using gsk2795039

1

Alzheimer's Disease Mouse Model Treatment

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Drugs were administered 1-month post-surgery to avoid surgery side effects. Mice were allocated to three groups: control (n = 6), Aβ (n = 5), and Aβ + GSK2795039 (n = 6). Injections were made i.c.v. through the guide cannula (1 μl/min) to awake mice. All substances were injected in equal volumes (1 μl) and the guide cannula was closed by a plunger. Mice in the Aβ + GSK2795039 group received GSK2795039 (MedChemExpress Europe; 4.5 mg/ml in DMSO) and oligomeric Aβ1-42 (Sigma-Aldrich, 1 mg/ml in 1.0% NH4OH) on the first day, and daily GSK2795039 further for 14 days. Mice in the Aβ group received Aβ1-42 on the first day and daily DMSO for the following 14 days. Mice in the сontrol group received daily DMSO for 15 days.
Malkov A., Popova I., Ivanov A., Jang S.S., Yoon S.Y., Osypov A., Huang Y., Zilberter Y, & Zilberter M. (2021). Aβ initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice. Communications Biology, 4, 1054.
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2

Dexmedetomidine Modulates Monocyte Oxidative Stress

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Dexmedetomidine is obtained from Hengrui Medicine (Jiangsu, China). U937 monocytes are pretreated with dexmedetomidine (0.1 nM and 1 nM) for 24 hours before other experiments. NAC (Sigma-Aldrich, 10 mM, 1 hour) is used to scavenge ROS. GSK2795039 (MedChemExpress, NJ, USA, 25 μM, 24 hours) is used to inhibit NOX2. Gö6976 (Cell Signaling Technology, Danvers, MA, USA, 10 μM, 24 hours) is used to inhibit PKC-α.
Chai Y., Cao Z., Yu R., Liu Y., Yuan D, & Lei L. (2020). Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes. Oxidative Medicine and Cellular Longevity, 2020, 2930463.
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3

Multiparametric Cellular Oxidative Stress Assay

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The following reagents were obtained: Hoechst 33342, 2,4-dinitrophenol (DNP), and L-012 (Sigma-Aldrich, St. Louis, MO); diphenyleneiodonium chloride (DPI; Abcam, Cambridge, United Kingdom); GSK2795039 (MedChemExpress, Monmouth Junction, NJ); anti-CD15 AF647, anti-myeloperoxidase (MPO) phycoerythrin (PE), and anti-rabbit secondary antibody BV421 (BD Biosciences, San Jose, CA); and CellROX, MitoSOX, dihydrorhodamine 123 (DIH123), 3,3′-dihexyloxacarbocyanine iodide (DiOC6), and Sytox Green (nucleic acid stain; Invitrogen, Carlsbad, CA).
Leung H.H., Perdomo J., Ahmadi Z., Yan F., McKenzie S.E, & Chong B.H. (2021). Inhibition of NADPH oxidase blocks NETosis and reduces thrombosis in heparin-induced thrombocytopenia. Blood Advances, 5(23), 5439-5451.
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4

Biochemical Reagents for Cell Studies

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Bacterial lipopolysaccharide (LPS), iodoacetic acid (IAA), 2-deoxyglucose (2DG), indomethacin, 2-thenoyltrifluoroacetone (TTFA), oligomycin, rotenone, antimycin A and myxothiazol were from Sigma Aldrich (St. Louis, MO, USA). GKT137831, zileuton, PD146176, idebenone, piericidin A, trifluoromethoxy carbonylcyanide phenylhydroazone (FCCP), S-ethyl isothiourea (SEITU) and 1400W were from Cayman Chemical (Ann Arbor, MI, USA). GSK2795039 was from MedChem Express (Monmouth Junction, NJ, USA). All other chemicals were from Sigma Aldrich.
, & Maher P. (2021). Investigations into the Role of Metabolism in the Inflammatory Response of BV2 Microglial Cells. Antioxidants, 10(1), 109.
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5

Quantifying Parasite Growth and ROS/Cytokine Rescue

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For the growth assay, parasite growth rate was determined using previously described methods which employ a direct parasite-per-vacuole scoring approach (69 (link)). Briefly, freshly syringe-lysed parasites (MOI 1) were added to confluent HFF monolayers grown on glass coverslips and spun down at 300 rpm for 1 min. After 1 h, the cultures were then washed to remove noninvaded parasites. At 24 hpi, infected monolayers were fixed, permeabilized, and stained with anti-SAG1 antibodies (as above) and then analyzed by fluorescence microscopy to identify the number of parasites per vacuole. One hundred vacuoles per coverslip were analyzed. For ROS rescue assays, HFFs were treated with either 5 mM N-acetyl-l-cysteine (Abcam, ab139473), 25 μM GSK2795039 (MedChemExpress, 1415925-18-6), or 10 μM Necrox-5 (Cayman Chemical, no. 17278) at the time of infection for either 6 or 24 hpi. Cells were then fixed, stained, and quantified as above. For cytokine rescue assays, HFFs were treated with 100 ng of recombinant human IL-4 or IL-6 (Sigma-Aldrich numbers I4269 and #I2786) at the time of infection to more closely mimic ROP16 injection. Cells were then fixed, stained, and quantified as above.
Kochanowsky J.A., Thomas K.K, & Koshy A.A. (2021). ROP16-Mediated Activation of STAT6 Suppresses Host Cell Reactive Oxygen Species Production, Facilitating Type III Toxoplasma gondii Growth and Survival. mBio, 12(2), e03305-20.
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6

Investigating NOX2 and ATM Inhibitors

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Nitazoxanide and Clotrimazole were obtained from Selleckchem and solubilized in DMSO (used as vehicle control in all experiments with these compounds). Ultrapure LPS for cell culture experiments (Lipopolysaccharide from Escherichia coli 0111:B4) was purchased from Invivogen. NOX2 inhibitor GSK2795039 was obtained from MedChem Express. ATM inhibitor KU-55933 was from Cell Signaling Technology.
Purandare N., Kunji Y., Xi Y., Romero R., Gomez-Lopez N., Fribley A., Grossman L.I, & Aras S. (2022). Lipopolysaccharide induces placental mitochondrial dysfunction in murine and human systems by reducing MNRR1 levels via a TLR4-independent pathway. iScience, 25(11), 105342.
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7

Investigating Nox2/Nox4 Signaling in Cell Apoptosis

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Western blot was performed using the following primary antibodies: anti-human Nox2, anti-human Nox4 (BD Biosciences, San Diego, CA, USA), and anti-human β-actin antibodies (Santa Cruz Biotechnology, Santa Cruz, CA, USA). GSK2795039, a Nox2 inhibitor, was obtained from MedChemExpress (Monmouth Junction, NJ, USA). Anti-human caspase 3 and 9 antibodies (Abcam, Cambridge, MA, USA) and anti-human Mcl-1, Bcl-2, Bim, Noxa antibodies (Cell Signaling Technology, Beverly, MA, USA) were used to evaluate protein expression. N-Benzyloxycarbonyl-Val-Ala-Asp (O-Me) fluoromethyl ketone (Z-VAD-FMK, Sigma, St. Louis, USA), a pan-caspase inhibitor; N-acetyl-L-cysteine (NAC, Cell Signaling Technology), a ROS scavenger; and ABT-263 (Selleck Chemical, Shanghai, China), a Bim specific inhibitor were used to identify the intra-cellular signaling pathway.
Ryu C.H., Kim S.H, & Hur D.Y. (2020). Nicotinamide adenine dinucleotide phosphate oxidase inhibitor induces apoptosis on Epstein-Barr virus positive B lymphoma cells. Anatomy & Cell Biology, 53(4), 471-480.
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8

Chemical Reagents for Experimental Protocols

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GKT137839 was obtained from Cayman Chemicals (Ann Arbor, MI, USA); GSK2795039 was from MedChemExpress (Monmouth Junction, NJ, USA) and all other chemicals were from Sigma (St. Louis, MO, USA), unless otherwise specified.
de Oliveira M.G., Monica F.Z., Passos G.R., Victorio J.A., Davel A.P., Oliveira A.L., Parada C.A., D’Ancona C.A., Hill W.G, & Antunes E. (2022). Selective Pharmacological Inhibition of NOX2 by GSK2795039 Improves Bladder Dysfunction in Cyclophosphamide-Induced Cystitis in Mice. Antioxidants, 12(1), 92.
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9

Antagonist of NMDA Receptor Assay

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Antagonist of NMDA receptors, (2R)-amino-5-phosphonopentanoate (APV) was purchased from Tocris Bioscience; GSK2795039 from MedChemExpress.
Malkov A., Popova I., Ivanov A., Jang S.S., Yoon S.Y., Osypov A., Huang Y., Zilberter Y, & Zilberter M. (2021). Aβ initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice. Communications Biology, 4, 1054.
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