Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Effect of ring substitution at the p-position on the binding affinity of anilides of the xanthine carboxylic congener (XCC) as adenosine receptor antagonists. The p-cyano analog is MRS 1754 [Kim et al., 2000b]. Ki values at the following human ARs are shown: A1(■), A2A (✦), A2B (●), and A3 (▲).

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Use of 1,4-dihydropyridines as a molecular template for antagonists of the human A3AR. Representative members of a library of DHP derivatives and their affinity (Ki in μM) in binding to the human A3AR are shown [Jiang et al., 1998].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Use of 3,5-diacylpyridine derivatives, prepared by oxidation of the corresponding DHPs, as a molecular template for antagonists of the human A3AR. Representative members of a library of such pyridine derivatives and their affinity (Ki in μM) in binding to the human A3AR are shown [Li et al., 1999].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: A prodrug scheme for the oxidative generation of pyridinium salts which act as antagonists of the human A3AR from the corresponding 1-alkyldihydropyridine derivatives. Such antagonists are highly water-soluble in contrast to most other classes of A3AR antagonists, which are hydrophobic [Xie et al., 1999].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques:

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Structural modifications of the adenosine moiety of P2Y1 receptor antagonists [Nandanan et al., 1999, 2000; Kim et al., 2000a]. The endogenous agonists of P2 receptors are nucleotides; however, bisphosphate analogs which act as antagonists have been identified. IC50 values at the turkey erythrocyte P2Y1 receptor for antagonism of phospholipase C activation by 30 nM 2-methylthio-adenosine 5′-diphosphate are indicated.

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Activation Assay

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: Effect of CF102 on the development of Con. A-induced hepatitis in mice. Acute hepatitis was induced in mice by I.V. injection of Con.A. CF102 (100 μg/kg) was administered orally twice daily, starting 8 h after Con. A injection. Serum levels of liver enzymes were measured 21 h after Con. A injection. CF102 markedly decreased SGOT and SGPT levels in comparison to the vehicle-treated group (P < 0.05).

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Comparison

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 protected the liver tissue from Con. A-induced damage. Acute hepatitis was induced in mice by I.V. injection of Con.A. Tissue sections of the livers were withdrawn from the mice 21 h after Con. A injection, fixed in formalin and subjected to H&E staining. In the vehicle-treated group, an extensive area of necrosis was observed while in the CF102-treated group no sign of necrosis was noted.

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Staining

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 acted as an anti-inflammatory agent in Con. A-induced hepatitis. Acute hepatitis was induced in mice by I.V. injection of Con.A. Liver tissues were collected 21 h later and protein extracts were derived from naïve- and Con. A-induced hepatitis mice were subjected to WB analysis. CF102 treatment induced (A) down-regulation in the expression levels of phosphorylated GSK-3β while the total GSK-3β expression levels remained almost unchanged in comparison to the vehicle-treated group. B: Down-regulation in the expression levels of the pro-inflammatory proteins NF-κB and TNF-α in comparison to the vehicle-treated group P < 0.05).

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Derivative Assay, Expressing, Comparison

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 prevented apoptosis in the liver upon Con. A-induced hepatitis. Acute hepatitis was induced in mice by I.V. injection of Con.A. Liver tissue was collected 21 h later and protein extracts from derived from naïve- and Con. A-induced hepatitis mice were subjected to WB analysis. CF102 treatment induced down-regulation in the pro-apoptotic proteins FasR, Bax, and Bad in comparison to the vehicle-treated group (P = 0.05).

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Derivative Assay, Comparison

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 inhibits the proliferation of human HCC Hep-3B cells. Hep-3B cells were incubated for 48 h with CF102 at concentrations of 1 and 10 nM. 3[H]-thymidine incorporation assay revealed that CF102 inhibited linearly the proliferation of the Hep-3B cells.

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Incubation, Thymidine Incorporation Assay

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: Modulation of A3AR expression levels in Hep-3B treated with CF102. Hep-3B cells were incubated for 48 h with CF102 at a concentration of 10 nM. Protein extracts derived from the Hep-3B cells were subjected to WB analysis. CF102 treatment resulted in down-regulation of A3AR expression levels.

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Expressing, Incubation, Concentration Assay, Derivative Assay

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: Modulation of down-stream signaling proteins expression levels in Hep-3B treated with CF102. Hep-3B cells were incubated for 48 h with CF102 at a concentration of 10 nM. Protein extracts derived from the Hep-3B cells were subjected to WB analysis. CF102 treatment induced down-regulation of PI3K, PKB/Akt, and NF-κB expression levels and increased the expression levels of the pro-apoptotic protein caspase-3.

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Expressing, Incubation, Concentration Assay, Derivative Assay

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 inhibited the development of Hep-3B tumors in a xenograft model. Hep-3B cells were injected subcutaneously into the flank of balb/c nude mice. Oral treatment with CF102 (100 μg/kg, three times per day) was initiated when the tumor reached ~50–100 mm3 in size and lasted until study termination. A: CF102 treatment inhibited tumor growth in comparison to the vehicle-treated group. B,C: At the end of the study an inhibition of 46% in tumor volume was observed in the CF102-treated group (P < 0.05).

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Comparison, Inhibition

Journal: Journal of cellular physiology

Article Title: CF102 an A 3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

doi: 10.1002/jcp.22593

Figure Lengend Snippet: CF102 up-regulated the apoptotic pathway in Hep-3B tumor cells. Hep-3B cells were injected subcutaneously into the flank of Balb/c nude mice. Oral treatment with CF102 (100 μg/kg, three times per day) was initiated when the tumor reached ~50–100 mm3 in size and lasted until study termination. Upon study termination, the tumors were excised and subjected to WB analysis. CF102 treatment induced up-regulation in the expression levels the pro-apoptotic proteins FasR, caspase-8, Bax, Bad, cytochrome-c, and caspase-3 in comparison to the vehicle-treated group (P = 0.05).

Article Snippet: Reagents The A 3 AR agonist CF102 (2-chloro- N 6 -(3-iodobenzyl)-adenosine-5′- N -methyl-uronamide, also known as Cl-IB-MECA), was synthesized for Can-Fite BioPharma by Albany Molecular Research, Inc., Albany, NY.

Techniques: Injection, Expressing, Comparison