a3ar agonist cl ib meca  (Tocris)

Journal: International Journal of Molecular Medicine

Article Title: The A3 adenosine receptor agonist, namodenoson, ameliorates non-alcoholic steatohepatitis in mice

doi: 10.3892/ijmm.2019.4364

Figure Lengend Snippet: Namodenoson reduces NAS and elevates adiponectin in the STAM model. Streptozotocin-injected mice were fed a high-fat diet and Namodenoson or the vehicle (DMSO) were administered p.o. thrice daily (200 µ g/kg) during weeks 6-9. (A) Representative liver sections of H&E staining demonstrating an improvement in steatosis, inflammation and ballooning in the Namodenoson-treated group vs. the vehicle. (B) Effects of Namodenoson on NAS. (C) Immunohistochemical staining depicting an increase in adiponectin upon Namodenoson treatment. The data represent the means ± SEM. Statistical analysis was carried out using a two-tailed Student's t-test. * P<0.05, ** P<0.01, Namodenoson vs. vehicle; n=8-14 animals/group. [Hematoxylin and eosin (H&E) staining: Original magnification, ×100]; adiponectin staining: Original magnification, ×40. NAS, non-alcoholic fatty liver disease (NAFLD) activity score.

Article Snippet: The A3AR agonist, Namodenoson, is a compound known generically as 2-chloro-N6-(3-iodobenzyl)-adenos ine-5′-N-methyl-uronamide, was synthesized for Can-Fite BioPharma by Albany Molecular Research Inc. A stock solution of 5.44 mg/ml was prepared in DMSO and further diluted in PBS for the in vivo and in vitro experiments.

Techniques: Injection, Staining, Immunohistochemical staining, Two Tailed Test, Activity Assay

Journal: International Journal of Molecular Medicine

Article Title: The A3 adenosine receptor agonist, namodenoson, ameliorates non-alcoholic steatohepatitis in mice

doi: 10.3892/ijmm.2019.4364

Figure Lengend Snippet: Namodenoson ameliorates liver functions and pathology via the deregulation of the Wnt/β-catenin pathway in the CCl4 model. CCL4-injected mice were treated twice weekly via i.p. injection with Namodenoson (100 µ g/kg) or the vehicle (DMSO). The levels of (A) serum ALT and (B) ascites were reversed to those of the naïve group following treatment with Namodenoson. (C) Representative stained liver sections demonstrating an improvement in inflammation (H&E staining), fibrosis (Sirius Red staining), adiponectin and leptin (immunohistochemistry); original magnification, ×40 (D) Representative western blots of the protein expression of A3AR, PI3K, GSK-3β, β-catenin and cyclin-D1 in mouse liver extracts. β-Actin served as an internal control. (E) mRNA expression of α-SMA. The data represent the means ± SEM. Statistical analysis was carried out by one-way ANOVA followed by Tukey's post-hoc analysis in panels A, C and E. The Chi-squared test was used for ascite assessment in panel B; * P<0.05, ** P<0.01, vehicle vs. naïve and Namodenoson vs. vehicle; n=8 animals/group. A3AR, A3 adenosine receptor; PI3K, phosphoinositide 3-kinase; GSK-3β, glycogen synthase kinase 3β; α-SMA, α-smooth muscle actin.

Article Snippet: The A3AR agonist, Namodenoson, is a compound known generically as 2-chloro-N6-(3-iodobenzyl)-adenos ine-5′-N-methyl-uronamide, was synthesized for Can-Fite BioPharma by Albany Molecular Research Inc. A stock solution of 5.44 mg/ml was prepared in DMSO and further diluted in PBS for the in vivo and in vitro experiments.

Techniques: Injection, Staining, Immunohistochemistry, Western Blot, Expressing, Control

Journal: International Journal of Molecular Medicine

Article Title: The A3 adenosine receptor agonist, namodenoson, ameliorates non-alcoholic steatohepatitis in mice

doi: 10.3892/ijmm.2019.4364

Figure Lengend Snippet: Namodenoson induces the proliferation inhibition and modulation of cell growth regulatory proteins in LX-2 HSCs. Cells were incubated for 48 h with the vehicle, Namodenoson (10 nM), the A3AR antagonist, MRS 1523 (5 nM), and a combination of the agonist and the antagonist. (A) Cell proliferation. The data represent the means ± SEM. Statistical analysis was carried out by one-way ANOVA followed by Tukey's post-hoc analysis. ** P<0.01, vehicle vs. Namodenoson; 4 independent experiments. (B) Western blot analyses of A3AR, PI3K, NF-κB and α-SMA. (C) Western blot analyses of β-catenin, GSK-3β, LEF-1 and cyclin D1; β-actin was used as a loading control. (D) α-SMA mRNA expression examined by RT-qPCR. A3AR, A3 adenosine receptor; PI3K, phosphoinositide 3-kinase; GSK-3β, glycogen synthase kinase 3β; LEF-1, lymphoid enhancer-binding factor 1; α-SMA, α-smooth muscle actin.

Article Snippet: The A3AR agonist, Namodenoson, is a compound known generically as 2-chloro-N6-(3-iodobenzyl)-adenos ine-5′-N-methyl-uronamide, was synthesized for Can-Fite BioPharma by Albany Molecular Research Inc. A stock solution of 5.44 mg/ml was prepared in DMSO and further diluted in PBS for the in vivo and in vitro experiments.

Techniques: Inhibition, Incubation, Western Blot, Control, Expressing, Quantitative RT-PCR, Binding Assay

Journal: International Journal of Molecular Medicine

Article Title: The A3 adenosine receptor agonist, namodenoson, ameliorates non-alcoholic steatohepatitis in mice

doi: 10.3892/ijmm.2019.4364

Figure Lengend Snippet: Proposed mechanism confers the anti-NASH effect of Namodenoson in the liver. Namodenoson via A3AR, downregulates the key protein PI3K, deregulates the NF-κB and the WNT signaling pathways, as well as α-SMA, leading to the inhibition of proliferation, inflammation, steatosis and fibrosis. The latter is also inhibited by adiponectin which is upregulated upon the inhibition of PI3K. The GSK3-β expression level is also increased, affecting as well the decrease of steatosis, altogether resulting in NAS inhibition. A3AR, A3 adenosine receptor; PI3K, phosphoinositide 3-kinase; GSK-3β, glycogen synthase kinase 3β; LEF-1, lymphoid enhancer-binding factor 1; α-SMA, α-smooth muscle actin; NAS, non-alcoholic fatty liver disease (NAFLD) activity score.

Article Snippet: The A3AR agonist, Namodenoson, is a compound known generically as 2-chloro-N6-(3-iodobenzyl)-adenos ine-5′-N-methyl-uronamide, was synthesized for Can-Fite BioPharma by Albany Molecular Research Inc. A stock solution of 5.44 mg/ml was prepared in DMSO and further diluted in PBS for the in vivo and in vitro experiments.

Techniques: Protein-Protein interactions, Inhibition, Expressing, Binding Assay, Activity Assay

Journal: Journal of Clinical and Translational Hepatology

Article Title: Future Pharmacotherapy for Non-alcoholic Steatohepatitis (NASH): Review of Phase 2 and 3 Trials

doi: 10.14218/JCTH.2017.00056

Figure Lengend Snippet: Active phase 2 clinical trials for the pharmacologic treatment of NASH registered on ClinicalTrials.gov

Article Snippet: CF102 , A3AR agonist , (NCT02927314; Can-Fite BioPharma, Petah-Tikva, Israel) , Feb 2018 , 60 , ≤40 , Absence of cirrhosis (Fibroscan score ≤F4 + LSM of 7.13 kPa) , NMRS , Percent change in the liver triglyceride concentration on NMRS at 12 weeks Adverse events at 12 weeks.

Techniques: Clinical Proteomics, Variant Assay, Imaging, Concentration Assay