Abstract: The present invention concerns an A3 adenosine receptor (A3AR) ligand for use in the treatment of an advanced solid tumor, e.g., hepatocellular carcinoma (HCC) in a mammalian subject.

Abstract: Cannabinoids are used to treat diseases or disorders treatable by an activator of the A3 adenosine receptor (A3AR). The cannabinoid effect is exerted through the A3AR. The cannabinoids may be selected from natural, phytocannabinoids, synthetic derivatives of phytocannabinoids, extracts of cannabis plant, and others.

Abstract: Provided is an A3AR ligand for reducing ectopic fat accumulation, particularly in fatty liver. Further provided is the use of A3AR ligand for the preparation of a pharmaceutical composition for reducing such fat accumulation, method of treating a condition associates with fat accumulation making use of the ligand and kits including pharmaceutical compositions including the ligand, and instructions for use of same, for treating a condition associated with ectopic fat accumulation. Further provided is the use of an A3AR agonist, such as 2-Chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyluronamide (CI-IB-MECA, CF102) for treating fatty liver, specifically, non-alcoholic fatty liver disease (NAFLD).

Abstract: Provided is an A3 adenosine receptor (A3AR) ligand for use in achieving at least one fat loss effect selected from: reducing weight of the subject; reducing body fat mass in the subject; treating obesity in the subject and inhibiting adipocytes proliferation in a subject. The disclosure also concerns pharmaceutical compositions, methods of treatment and kits comprising the A3AR ligand.

Abstract: Provided is a method of managing cytokine release syndrome (CRS) in a subject undergoing immunotherapy treatment, the method includes administering to the subject an amount of an A3 adenosine receptor (A3AR) ligand effective to manage one or more of (i) level of at least one inflammatory cytokine and (ii) at least one CRS symptom; wherein the management is without significantly affecting the immunotherapy treatment. Also provided is an A3AR ligand and a composition including the ligand for use in the management of cytokine release syndrome (CRS) in a subject undergoing immunotherapy treatment, the management includes one or more of (i) managing level of at least one inflammatory cytokine and (ii) managing at least one CRS symptom; wherein the management is without significantly affecting the immunotherapy treatment.

Abstract: Provided is an A3AR ligand for reducing ectopic fat accumulation, particularly in fatty liver. Further provided is the use of A3AR ligand for the preparation of a pharmaceutical composition for reducing such fat accumulation, method of treating a condition associates with fat accumulation making use of the ligand and kits including pharmaceutical compositions including the ligand, and instructions for use of same, for treating a condition associated with ectopic fat accumulation. Further provided is the use of an A3AR agonist, such as 2-Chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyluronamide (CI-IB-MECA, CF102) for treating fatty liver, specifically, non-alcoholic fatty liver disease (NAFLD).

Abstract: Provided is an A3AR ligand for reducing ectopic fat accumulation, particularly in fatty liver. Further provided is the use of A3AR ligand for the preparation of a pharmaceutical composition for reducing such fat accumulation, method of treating a condition associates with fat accumulation making use of the ligand and kits including pharmaceutical compositions including the ligand, and instructions for use of same, for treating a condition associated with ectopic fat accumulation. Further provided is the use of an A3AR agonist, such as 2-Chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyluronamide (Cl-IB-MECA, CF102) for treating fatty liver, specifically, non-alcoholic fatty liver disease (NAFLD).

Abstract: Provided is an A3 adenosine receptor agonist (A3AR agonist) for the preparation of a pharmaceutical composition for the treatment of a mammal subject having osteoarthritis (OA), as well as to a method for the treatment of OA in a mammal subject, the method includes administering to said subject in need of said treatment an amount of A3AR agonist, the amount being effective to treat or prevent the development of OA. Preferred but not exclusive A3AR agonists in accordance with the present subject matter are IB-MECA and Cl-IB-MECA. The A3AR agonist may be administered in combination with another drug, such as Methotrexate (MTX). Also provided are pharmaceutical compositions for treatment of osteoarthritis including an amount of an A3AR agonist.

Abstract: Provided is an A3AR ligand for reducing ectopic fat accumulation, particularly in fatty liver. Further provided is the use of A3AR ligand for the preparation of a pharmaceutical composition for reducing such fat accumulation, method of treating a condition associates with fat accumulation making use of the ligand and kits including pharmaceutical compositions including the ligand, and instructions for use of same, for treating a condition associated with ectopic fat accumulation. Further provided is the use of an A3AR agonist, such as 2-Chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyluronamide (Cl-IB-MECA, CF102) for treating fatty liver, specifically, non-alcoholic fatty liver disease (NAFLD).

Abstract: The present disclosure provides an A3 adenosine receptor (A3AR) ligand for the treatment of sexual dysfunction. In some embodiments the A3AR ligand is selected from an A3AR agonist and A3AR allosteric enhancer. The present disclosure also provides a method a method and pharmaceutical composition for treating a sexual dysfunction, the method comprises administering to a subject having the sexual dysfunction an amount of an A3 adenosine receptor (A3AR) ligand. In some embodiments, the A3AR ligand is an A3AR agonist and more specifically, IB-MECA.

Abstract: Provided is an A3 adenosine receptor agonist (A3AR agonist) for the preparation of a pharmaceutical composition for the treatment of a mammal subject having osteoarthritis (OA), as well as to a method for the treatment of OA in a mammal subject, the method includes administering to said subject in need of said treatment an amount of A3AR agonist, the amount being effective to treat or prevent the development of OA. Preferred but not exclusive A3AR agonists in accordance with the present subject matter are IB-MECA and Cl-IB-MECA. The A3AR agonist may be administered in combination with another drug, such as Methotrexate (MTX). Also provided are pharmaceutical compositions for treatment of osteoarthritis including an amount of an A3AR agonist.

Abstract: The present application provides methods and compositions for inducing hepatocyte proliferation and liver regeneration, the latter being mainly dependent on hepatocyte proliferation even if all the other cell types divide to reconstitute the organ specific-lobular-architecture. The methods and compositions provided herein make use of an A3AR agonist. A preferred A3AR agonist disclosed herein is Cl-IB-MECA.

Abstract: The present disclosure provides a method for the synthesis of IB-MECA. More specifically, the present disclosure provides a simple and high yield method for Good Manufacturing Production (GMP) of IB-MECA. The method involves the reaction of 6-halopurine-9-riboside with a diol protecting reagent; oxidation of the primary alcohol in the diol protected 6-halopurine-9-riboside with a diol protecting reagent; oxidation of the primary alcohol in the diol protected 6-halopurine; reaction of the diol protected 6-halopurine with a nucleophile (e.g. methylamine); substitution of the halogen group with iodobenzylamine and removal of the diol protecting group.

Abstract: The present disclosure provides an A3 adenosine receptor (A3AR) ligand for the treatment of sexual dysfunction. In some embodiments the A3AR ligand is selected from an A3AR agonist and A3AR allosteric enhancer. The present disclosure also provides a method a method and pharmaceutical composition for treating a sexual dysfunction, the method comprises administering to a subject having the sexual dysfunction an amount of an A3 adenosine receptor (A3AR) ligand. In some embodiments, the A3AR ligand is an A3AR agonist and more specifically, IB-MECA.

Abstract: Clinical finding shows that twice daily administrations of 2 mg of 1-deoxy-1-[N6-(3-iodobenzyl)-adenin-9-yl]-N-methyl-?-D-ribofuronamide (IB-MECA) (total daily administration of 4 mg) to subjects having moderate to severe psoriasis, was significantly more effective in treatment of the psoriatic plaques than treatment of psoriasis at two administration doses of 1 mg or 4 mg (total daily doses of 2 or 8 mg, respectively). A pharmaceutical composition for the treatment of psoriasis includes as the active ingredient IB-MECA in an amount suitable for a total daily dose administration of about 4 mg. In one preferred embodiment, IB-MECA is administered twice a day to a subject in need of psoriasis treatment, the pharmaceutical composition including an administration dose of 2 mg.

Abstract: The present application provides methods and compositions for inducing hepatocyte proliferation and liver regeneration, the latter being mainly dependent on hepatocyte proliferation even if all the other cell types divide to reconstitute the organ specific-lobular-architecture. The methods and compositions provided herein make use of an A3AR agonist. A preferred A3AR agonist disclosed herein is Cl-IB-MECA.

Abstract: Inflammatory state in a subject is assayed by determining the level of expression of A3 adenosine receptor (A3AR) in white blood cells (WBC), e.g. circulating WBCs, from the subject. A high level of expression of A3AR is indicative of an inflammatory state in the subject. This assay can be used for determining whether a patient known to have an inflammatory state should be treated with an A3AR agonist to reduce the inflammatory state. The patient will be so treated only if the level of A3AR in the WBC of the subject is above a predefined threshold, which is about twice the level of A3AR in WBC of healthy subjects. The inflammatory state may particularly be rheumatoid arthritis or uveitis.

Abstract: The present disclosure provides the use of an A3R agonist, such as IB-MECA, for reducing in a subject, preferably, human subject, intra ocular pressure (IOP). Similarly, the invention provides a pharmaceutical composition and a method for reducing IOP in a subject making use of the A3R agonist.

Abstract: Inflammatory state in a subject is assayed by determining the level of expression of A3 adenosine receptor (A3AR) in white blood cells (WBC), e.g. circulating WBCs, from the subject. A high level of expression of A3AR is indicative of an inflammatory state in the subject. This assay can be used for determining the severity of inflammation in a subject and monitoring the efficacy of anti-inflammatory treatment. Also, the level of expression may be used for selecting patients to receive an anti-inflammatory treatment that comprises an A3AR agonist.

Abstract: The present invention is based on the clinical finding that twice daily administrations of 2 mg of 1-[N6-(3-iodobenzyl)-adenin-9-yl]-?-D-ribofuronamide (IB-MECA) (total daily administration of 4 mg) to subjects having moderate to severe psoriasis, was significantly more effective in treatment of the psoriatic plaques than treatment of psoriasis at two administration doses of 1 mg or 4 mg (total daily doses of 2 or 8 mg, respectively). Thus, the present invention provides a pharmaceutical composition for the treatment of psoriasis comprising as the active ingredient IB-MECA in an amount suitable for a total daily dose administration of about 4 mg. In one preferred embodiment IB-MECA is administered twice a day to a subject in need of psoriasis treatment, the pharmaceutical composition comprising an administration dose of 2 mg.