Journal: Biochemistry and Biophysics Reports

Article Title: Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

doi: 10.1016/j.bbrep.2020.100832

Figure Lengend Snippet: JAK2 inhibitors inhibit proliferation, while JAK1/3 inhibitors do not. A-D: SeAx cells were seeded at a cell density of 50,000 cells per well in a 96 wells plate. After incubation for 48 h with AZD1480, decernotinib, ruxolitinib and tofacitinib, viability was quantitated. E: IC 50 values were determined for AZD1480 and ruxolitinib. Error bars represent SD of three separate experiments. ****P < 0.0001 versus AZD1480.

Article Snippet: JAK inhibitors (JAKi) AZD1480 (Tocris, Bristol, UK), decernotinib (MedChem Express, Monmouth Junction, NJ), ruxolitinib (Selleck, Houston, TX) and tofacitinib (Pfizer, Capelle a/d Ijssel, The Netherlands) were dissolved in DMSO to a concentration of 10 mM.

Techniques: Incubation

Journal: Frontiers in Neurology

Article Title: Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice

doi: 10.3389/fneur.2017.00363

Figure Lengend Snippet: (A) Dose–response curves measuring infarct volume in vehicle-treated and 0.03, 0.1, 0.3, 3, and 10 mg/kg of decernotinib-treated mice. There was no significant difference in infarct size across groups (vehicle, n = 8; 0.03 mg/kg, n = 6; 0.1 mg/kg, n = 8; 0.3 mg/kg, n = 8; 3 mg/kg, n = 10; and 10 mg/kg, n = 8). Data were analyzed using a one-way ANOVA with a Dunnett’s multiple comparison post-test. (B) Representative 2,3,5-triphenyl-tetrazolium chloride (TTC) images of vehicle- and 10 mg/kg decernotinib-treated mice to show extent of cortical injury in our model of permanent middle cerebral artery occlusion (MCAO). (C) Representative immunoblots of brain tissue obtained from the ipsilateral (CXI) and contralateral (CXC) cerebral cortex depicting reduced phosphorylation of Janus kinase 3 (JAK3) in the 10 mg/kg decernotinib group compared to vehicle. There is no effect of decernotinib on stroke-induced increase in total JAK3 levels. (D,E) Graphical summary of immunoblot data (* P < 0.05 compared to vehicle ipsilateral; vehicle, n = 9; 10 mg/kg decernotinib, n = 5). Data were analyzed using a two-way ANOVA. (F) Latency to remove the sticky tape from the contralateral paw, measuring sensorimotor deficits, in vehicle and decernotinib groups. Stroke induced a significant increase in the latency to remove the sticker at 24 h in the vehicle-treated group. Comparing both treatments at 24 h, there was a trend toward a better performance in the adhesive removal test in mice given decernotinib, but this effect did not reach a statistical significance (two-way ANOVA with Bonferroni post-test; vehicle n = 9; decernotinib at a dose of 10 mg/kg, n = 10).

Article Snippet: Animals were treated with vehicle or 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg decernotinib (Cat # CT-DECE; ChemieTek, Indianapolis, IN, USA), a highly selective JAK3 inhibitor.

Techniques: Comparison, Western Blot, Phospho-proteomics, Adhesive

Journal: Frontiers in Neurology

Article Title: Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice

doi: 10.3389/fneur.2017.00363

Figure Lengend Snippet: (A) IL-21 is increased in the ipsilateral cortex compared to the contralateral cortex (** P < 0.01) (B) IL-4 does not appreciably change between treatment groups or hemisphere. (C) There is a trend toward increased IL-7 in the ipsilateral cortex. (D) There is no change in IL-9 between groups. (E) There is no change in IL-15 between groups. (F) There is no significant change in IL-2 across groups. (G) Ccl2 is significantly increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (*** P < 0.01). (H) Cxcl10 is significantly increased in the ipsilateral cortex in both groups (*** P < 0.01; ** P < 0.01). (I) Cxcl1 is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (*** P < 0.01). (J) IL-1 β is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (*** P < 0.01). (K) IL-6 is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (** P < 0.01; *** P < 0.01). (L) Tnfα is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (*** P < 0.01). (M) Ptgs2 is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (* P < 0.05; *** P < 0.01). (N) Mmp-9 is increased in the ipsilateral cortex in vehicle- and 10 mg/kg decernotinib-treated groups (** P < 0.01) Statistical analyses performed with a two-way ANOVA and Bonferroni post-test; vehicle n = 5, 10 mg/kg decernotinib, n = 7.

Article Snippet: Animals were treated with vehicle or 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg decernotinib (Cat # CT-DECE; ChemieTek, Indianapolis, IN, USA), a highly selective JAK3 inhibitor.

Techniques:

Journal: Frontiers in Neurology

Article Title: Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice

doi: 10.3389/fneur.2017.00363

Figure Lengend Snippet: (A) Representative immunoblot of mouse brain tissue. (B) Graphical summary of phosphorylated STAT3 immunoblot data normalized to actin (* P < 0.05; ** P < 0.01, vehicle n = 9; 10 mg/kg decernotinib, n = 5). Phosphorylated STAT3 is increased in the ipsilateral cortex compared to the contralateral. Phosphorylated STAT3 is decreased in the ipsilateral cortex with 10 mg/kg decernotinib compared to the vehicle-treated group. (C) Graphical summary of total STAT3 immunoblot data normalized to actin (vehicle, n = 9; 10 mg/kg decernotinib, n = 5). Total STAT3 does not vary between groups.

Article Snippet: Animals were treated with vehicle or 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg decernotinib (Cat # CT-DECE; ChemieTek, Indianapolis, IN, USA), a highly selective JAK3 inhibitor.

Techniques: Western Blot

Journal: International Journal of Molecular Sciences

Article Title: Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases

doi: 10.3390/ijms22062805

Figure Lengend Snippet: Approved and investigational biologics and small molecules for RA.

Article Snippet: SM , Decernotinib , Aclaris Therapeutics , Phase II , n/a , Oral.

Techniques: