Abstract: Disclosed are novel compounds a compound of Formula I that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular dyslipidemia, diabetes, decreased insulin sensitivity, Polycystic Ovarian Syndrome, Stein-Leventhal syndrome, and obesity.

Abstract: The present invention relates to the novel use of an adenosine aspartate product for the formulation of a drug intended to prevent the development of preneoplastic lesions and to reverse some types of cancer, particularly liver cancer, providing chemoprotection, preventing myelotoxic effects.

Abstract: A2A agonists of formula (I) is provided, wherein R1, R2, R4, R5, X, Y, Z, n, p, and q are as described herein. Also provided are compositions comprising and methods of using compounds of formula (I).

Abstract: The present invention comprises compounds useful as antiviral or antitumor agents. The compounds comprise nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moeities with quaternary centers at the 3? position. The nucleotide analogues can be used to inhibit cancer or viruses. Accordingly, the compounds of the present invention are useful for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses. Thus, the present invention also comprising pharmaceutical formulations comprising the compounds and methods of using the compounds and formulations to inhibit viruses or tumors and treat, prevent, or inhibit the foregoing diseases.

Abstract: Provided are methods of designing a putative inhibitor of a 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase. The methods comprise designing a chemically stable compound that resembles the charge and geometry of the 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase transition state. Also provided are methods of inhibiting 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidases using the inhibitors found by the above methods.

Abstract: Global DNA methylation is a predictor of aggressive disease in patients with chronic lymphocytic leukemia. The higher the DNA methylation, the more likely a patient is going to require systemic therapy. Although there is a gradual decline in global DNA methylation with increasing age in normal individuals, the methylation index only decreases by approximately 0.03 per decade. A pilot study was performed in which patients with chronic lymphocytic leukemia were treated with low doses of DNA methylation inhibitors to evaluate if inhibition of DNA methylation can translate into a clinical benefit. Inhibition of DNA methylation was observed to lead to re-expression of tumor suppressors and normal cellular function. At low non-toxic doses of 0.05-0.09 mg per kilogram per day for three days every 28 days, some patients with chronic lymphocytic leukemia were observed to achieve a reduction in circulating leukemia cells.

Abstract: The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof which inhibit HCV polymerase and are useful for treating a patient suffering from a HCV infection and to pharmaceutical compositions containing such compounds.

Abstract: Processes for the preparation of racemic and optically active nucleoside analogs of formula (A) are described. These compounds are useful as anti-infective agents, antisense therapeutic agents and hybridization assay probes.

Abstract: The present invention relates to a method of increasing blood brain barrier permeability in a subject. This method involves selecting a subject who would benefit from increased blood brain barrier permeability and subjecting the selected subject to a treatment. That treatment increases adenosine level and/or bioavailability, modulates adenosine receptors, and/or increases CD73 level and/or activity under conditions effective to increase blood brain barrier permeability in the subject. Methods of decreasing blood brain barrier permeability in a subject, treatment of a subject for a disorder or condition of the central nervous system, and screening compounds effective in increasing blood brain barrier permeability, as well as pharmaceutical agents are also disclosed.

Abstract: The present invention relates to a combination of therapeutic agents comprising: (a) a cytosine-based anti-cancer drug and/or a purine-based anticancer drug and (b) a therapeutic agent selected from the group consisting of thymidine phosphorylase inhibitors, and antibiotics against Mollicutes bacteria. The present invention also relates to the simultaneous, separate or sequential use of said combination for the treatment of cancer in mammals, especially in humans. The present invention also relates to methods of treatment of cancer, preferably in mammals infected with Mollicutes bacteria.

Abstract: Dietary supplement compositions are disclosed. Methods of making and using dietary supplement compositions are also disclosed.

Abstract: The invention relates to Purine Derivatives; compositions comprising an effective amount of a Purine Derivative; and methods for treating or preventing an ischemic condition, reperfusion injury, a cellular proliferative disorder, a cardiovascular disease, a neurological disorder, a skin disorder, a radiation-induced injury, a wound, or an inflammatory disease comprising administering an effective amount of a Purine Derivative to a subject in need thereof.

Abstract: The present invention provides novel crystalline polymorphic forms of 2-cyclohexylmethylidenehydrazino adenosine, also known as binodenoson, methods of making the same, and methods for the manufacture of a pharmaceutical composition by employing such crystal forms, in particular, for the use of binodenoson in a subject, in need thereof, as a pharmacological stress agent to produce coronary vasodilation.

Abstract: The present invention relates to fatty acid and fatty alcohol substituted nucleoside derivatives and nucleoside and nucleoside derivatives substituted on multivalent scaffolds (e.g., polymers, peptides, polycarboxylic acid substituted compounds, compounds containing polycycloSaligenyl groups) that display potent anti-HIV activity. Furthermore, they show enhanced activity against multi-drug resistant, R5, and cell-associated virus. Some of them also display activity against other sexually transmitted pathogens and sperm. The present invention provides their methods of synthesis, composition of matter, and methods of use. Emphasis is placed on their application as topical microbicides to treat or prevent sexual transmission of disease, especially HIV/AIDS.

Abstract: Provided are polymorphs of an A1 adenosine receptor partial agonist, compositions thereof, methods for their preparation, and methods for their uses.

Abstract: Provided are compositions of cladribine and cyclodextrin which are especially suited for the oral administration of cladribine.

Abstract: A2A agonists of formula (I) is provided, wherein R1, R2, R4, R5, X, Y, Z, n, p, and q are as described herein. Also provided are compositions comprising and methods of using compounds of formula (I).

Abstract: The invention relates to compositions and methods to enhance the absorption of S-adenosylmethionine (SAMe) and to methods of treating various disorders or diseases using non-parenteral SAMe formulations with enhanced-absorption and improved bioavailability. The enhanced bioavailability formulations may be used to treat a variety of diseases or disorders, such as for example, psychiatric disorders including, generalized anxiety disorder, obsessive compulsive disorder, post traumatic stress disorder, panic disorder, depressive disorders (e.g. major clinical depression) and dysthymia; as well as treating liver disorders, cancer, autoimmune disorders, inflammatory disorders, joint disorders, gastrointestinal disorders and cardiovascular disease.

Abstract: The invention relates to the use of alkylphosphocholines in combination with antimetabolites for the treatment of multiple myeloma, colon cancer or renal cancer. Preferred alkylphosphocholines are described by the Formula II. A particularly effective treatment includes administering a combination of perifosine and capecitabine.

Abstract: Compositions and methods to improve the pharmacokinetic profile of S-Adenosylmethionine (SAMe) are provided, as are methods of treating various disorders using SAMe formulations with improved pharmacokinetic profiles. More specifically, the invention is directed to methods of treating a disease or disorder in a subject and/or improving the nutritional status of a subject by administering formulations exhibiting improved pharmacokinetic profiles of exogenous SAMe. The method also includes the step of orally administering compositions of the invention to the subject once per day after overnight fast; that is prior to food intake in the morning.

Abstract: The present invention relates to a drug-containing polymeric composition comprising at least one therapeutic agent encapsulated in at least one biocompatible polymer, wherein at least a portion of the therapeutic agent in this polymeric composition is crystalline. The at least one biocompatible polymer may form a substantially continuous polymeric matrix with the at least one therapeutic agent encapsulated therein. Alternatively, the at least one biocompatible polymer may form polymeric particles with the at least one therapeutic agent encapsulated therein.

Abstract: A method is disclosed for treating and inducing the regression of established atherosclerotic plaques. A method is disclosed for treating asthma, including treatment of an ongoing asthma attack. In both cases, treatment with PARP inhibitors, such as the PARP inhibitor TIQ-A (Thieno[2,3-c]isoquinolin-5-one), can lead to regression of existing disease and symptoms.

Abstract: The invention provides a method of treating a cardiac disease by administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent, such as, for instance a ?-blocker. In some embodiments, the AC5 inhibiting compound is 9-?-D-arabinofuranosyladenine (AraAde). The compound may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered parenterally. The cardiac disease may be, for instance, myocardial infarction (MI) or heart failure (HF). The compound capable of inhibiting AC5 may be administered alone or in conjunction with one or more other active agents.

Abstract: Disclosed are methods of using proteasome inhibitors (PI) in combinations with other pharmaceutically active agents for treating viral hepatitis infections, for example, for treating therapy-resistant and -refractory viral hepatitis infections. Also disclosed are pharmaceutical compositions and kits of pharmaceutical compositions which can be used for treating viral hepatitis infections, for example, for treating therapy-resistant and refractory viral hepatitis infections.

Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.

Abstract: Disclosed is a compound and methods for use by an individual attempting to reduce or cease tobacco smoking or one exposed to environmental tobacco smoke. The compound includes a first component blocking nicotine receptor sites to reduce nicotine cravings or withdrawal symptoms, a second component increasing serotonin levels and acting synergistically with the first component to reduce nicotine cravings or withdrawal symptoms, assisting in maintaining body weight and reducing increased stress and anxiety, and a third component acting synergistically with the first and/or second component to reduce nicotine cravings or withdrawal symptoms, maintain body weight, and/or reduce increased stress and anxiety. The third component comprises a supplement that replenishes depleted body substance(s), repairs damaged body substance(s), and/or ameliorates the impaired function of body substance(s). Some combination of the first, second, and third component alters the perceived taste of tobacco smoke.

Abstract: Provided are compositions of cladribine and cyclodextrin which are especially suited for the oral and buccal administration of cladribine.

Abstract: The present invention relates to targets of loss of imprinting (LOI) affected IGF2 gene products in pre-malignant tissues, where methods of inhibiting those targets, including IGFR1, are disclosed to prevent tumor development in subjects at risk for developing colorectal cancer (CRC). The present invention also relates to methods of identifying increased risk in developing CRC in a subject, including methods of assessing the efficacy of a chemotherapeutic regimen. Further, the present invention relates to methods for identifying anti-neoplastic agents.

Abstract: The crystal structure of the complex of S-adenosylmethionine methyl ester with h?doMetDC F223A, a mutant where the stacking of the aromatic rings of F7, adenine and F223 would be eliminated. The structure of this mutant with the ester shows that the ligand still maintains a syn conformation aided by pi-pi interactions to F7, hydrogen bonds to the backbone of Glu67, and electrostatic interactions. Several series of AdoMet substrate analogues with a variety of substituents at the 8 position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. To understand these results, virtual modeling of the enzyme inhibitor complexes and the crystal structures of human AdoMetDC with 5?-deoxy-5?-[N-methyl-N-[2-(aminooxy)ethyl]amino-8-methyl]adenosine (MAOEMA) and 5?-deoxy-5?-[N-methyl-N-[4-(aminooxy)butyl]amino-8-ethyl]adenosine (MAOBEA) at the active site have been determined experimentally.

Abstract: This invention relates to novel compounds that are azapeptides, and pharmaceutically acceptable salts thereof. More specifically, the invention relates to novel azapeptide compounds that are derivatives of the HIV protease inhibitor atazanavir sulfate. This invention also provides pyrogen-free compositions comprising one or more compounds of the invention and a carrier, and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are treated by administering HIV protease inhibitors. The invention also relates to the use of one or more of the disclosed compounds as reagents in analytical studies involving atazanavir.

Abstract: Disclosed herein are compositions and methods for the treatment of skeletal muscle and/or the protection of skeletal muscle against injury. The adenosine A3 receptor has been identified as a new therapeutic target for the treatment of skeletal muscle. Adenosine A3 receptor agonists are used treat subjects with skeletal muscle ischemia and reperfusion (I/R) injuries, individuals with skeletal muscle disorders, and individuals suffering from skeletal muscle injury resulting from physical exertion.

Abstract: The present invention provides substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Abstract: Provided herein are alkoxy-carbonyl-amino-alkynyl-adenosine compounds and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Abstract: The invention relates to Purine Derivatives; compositions comprising an effective amount of a Purine Derivative; and methods for treating or preventing an ischemic condition, reperfusion injury, a cellular proliferative disorder, a cardiovascular disease, a neurological disorder, a skin disorder, a radiation-induced injury, a wound, or an inflammatory disease comprising administering an effective amount of a Purine Derivative to a subject in need thereof.

Abstract: In general, the invention features methods for identifying therapeutic interventions for functional illnesses, e.g., neuropathic pain or depression, and methods for identifying markers for functional illnesses by employing an acute painful stimulus or other stimulus for a functional illness and measuring levels of CNS activity.

Abstract: Methods for assessing a pathological condition in a subject include measuring one or more markers where a difference is indicative of acute lymphoblastic leukemia (ALL) or a predisposition to ALL, uses and compositions are disclosed.

Abstract: Methods are presented that comprise the administration of a pharmaceutical composition comprising adenosine and dipyridamole, as well methods comprising the combined administration of dipyridamole administered as a bolus with adenosine given as an infusion, both at dosages below their respective single agent dosages, for detecting the presence and/or assessing the severity of myocardial ischemia during pharmacologic stress tests. The methods are useful for exploiting the vasodilating abilities of adenosine at doses at which side effects related to adenosine are substantially reduced while optimal coronary artery perfusion is achieved. Also presented are compositions, unit dosage forms, and kits that are useful in performing the methods.

Abstract: This invention is directed to a method of enhancing or facilitating the clearance of the lung mucus secretions in a subject. This invention is also directed to a method of facilitating the hydration of the lung mucus secretions in a subject. This invention is further directed to a method of preventing or treating diseases or conditions associated with impaired lung or airway function in a human or other mammal. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y6 receptor agonist compound, wherein said amount is effective to activate the P2Y6 receptors on the luminal surface of lung epithelia. The P2Y6 receptor agonist compounds useful for this invention include mononucleoside 5?-diphosphates, dinucleoside monophosphate, dinucleoside diphosphates, or dinucleoside triphosphates of general Formula I, or salts, solvates, hydrates thereof.

Abstract: The present application describes deuterium-enriched nelarabine, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: A compound of Formula I, Formula II, Formula III, or Formula IV: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, therapeutic compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

Abstract: This invention relates to methods for promoting neuronal survival and regeneration using LINGO-1 antagonists and TrkB agonists. Additionally, the invention relates to methods for treating pressure induced optic neuropathies using LINGO-1 antagonists. The invention also relates generally to methods for increasing TrkB activity and inhibiting JNK pathway signaling using a LINGO-1 antagonist.

Abstract: The present invention relates to a method for arresting, protecting and/or preserving an organ which includes administering effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) local anaesthetic to a subject in need thereof. The present invention also relates to a method for arresting, protecting and/or preserving an organ which comprises adding a composition which includes effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) a local anaesthetic to the organ. The present invention further provides a pharmaceutical or veterinary composition which includes effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) a local anaesthetic.

Abstract: Compounds for modulating RecA protein activity are provided. In some embodiments, the compounds modulate RecA activity by interfering with assembly of monomeric RecA protein subunits into a nucleoprotein filament. In some embodiments, the compounds modulate RecA activity by interfering with adenosine triphosphate hydrolysis by the RecA protein. Methods of screening for and methods of using the compounds are also provided.

Abstract: Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof.

Abstract: The present invention relates to a method for preparing a 2-fluoropurine marked with the radioisotope 18F comprising a fluorination step for a 2-nitropurine derivative. The present invention comprises a 2-fluoropurine derivative marked with the radioisotope 18F which can be obtained by or during a method according to the invention and its various uses.

Abstract: The present invention relates to new indazole inhibitors of tyrosine kinase activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to a method of enhancing brain stimulation of a subject. This method involves selecting a subject in need of brain stimulation and electrically stimulating the brain of the subject. Adenosine, an adenosine mimetic, an adenosine modulator, an adenosine transport inhibitor, or an adenosine receptor agonist are administered to the subject under conditions effective to enhance electrical stimulation of the brain of the subject. The administration of adenosine, an adenosine mimetic, an adenosine modulator, an adenosine transport inhibitor, or an adenosine receptor agonist to the subject can alternatively be carried out with electrically stimulating the brain of the subject.

Abstract: The present invention relates to new benzimidazole modulators of H1 receptor activity and/or inhibitors of NS4B protein activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Riboswitches are targets for antibiotics and other small molecule therapies. Riboswitches and portions thereof can be used to regulate the expression or function of RNA molecules and other elements and molecules. Riboswitches and portions thereof can be used in a variety of other methods to, for example, identify or detect compounds. Compounds can be used to stimulate, active, inhibit and/or inactivate the riboswitch. Riboswitches and portions thereof, both alone and in combination with other nucleic acids, can be used in a variety of constructs and RNA molecules and can be encoded by nucleic acids.

Abstract: Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof.