Abstract: The present invention relates to novel pharmaceutical or cosmetic compositions comprising at least one inhibitor of a sub-unit of AP-1 adaptor complex, of a kinesin interacting with AP-1, in particular Kif13A, or of the interaction between a sub-unit of AP-1 adaptor complex and said kinesin, as well as the use of same to manufacture a drug intended for the treatment of pigmentary disorders and as a depigmentation agent.

Abstract: Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Abstract: The invention relates to methods and compositions for reducing blood glucose levels in hyperglycaemic subjects. The methods and compositions may therefore be suitable for treating a disease or condition associated with hyperglycaemia such as, for example, obesity (particularly diet induced obesity (DIO)), weight gain, Type II diabetes mellitus, insulin sensitivity, impaired glucose tolerance and inflammation. In some embodiments, the methods comprise administering a melanocortin-5 receptor (MC5R) agonist to one or more skeletal muscle cells of the subject. Preferred MC5R agonists are those that specifically activate MC5R and/or enhance expression of MC5R, such as the melanocortin analogue, Ac-Nle-c[Asp-Pro-D-Nal(2?)-Arg-Trp-Lys]-NH2.

Abstract: Disclosed herein are substituted fluoromethanes; pharmaceutical compositions comprising a therapeutically effective amount of the same; processes for preparing these fluoromethanes; and methods of using the same in alleviating infection and parasitism. Also disclosed are methods for identifying substituted fluoromethanes for modulating the activity of receptors and enzymes that bind and/or modify phosphate containing ligands and substrates.

Abstract: Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.

Abstract: Novel cap analogs which are easily synthesized, resulting in high levels of capping efficiency and transcription and improved translation efficiencies are provided. Such caps are methylated at the N7 position of one or both guanosines of the dinucleotide cap as well as at the 3? position on the ribose ring. Substituent groups on the ribose ring also result in the cap being incorporated in the forward orientation. Also provided are methods useful for preparing capped analogs and using mRNA species containing such analogs are also contemplated herein, as well as kits containing the novel cap analogs.

Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1?, 2? or 3?-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: Nutritional compositions and methods of making and using the nutritional compositions are provided. In a general embodiment, the present disclosure provides a nutritional composition including theanine and one or more exogenous nucleotides. The nutritional compositions can be specifically used to treat functional bowel disorders, including inflammatory bowel syndrome.

Abstract: The invention concerns the production of salts or chelates of methyl donors, in particular S-adenosyl-L-methionine or SAMe and betaine or N,N,N-trimethylglycine, with phytic acid or with phosphorylate inositol, possibly partially salified with metal cations, with the formation of stable, totally natural, compounds having a biological activity typical of the starting methyl donors and also combined with, and enhanced by, the biological activity typical of phytic acid or of inositol. The invention also concerns nutraceutical, pharmaceutical, dietary, phytopharmaceutical or veterinary compositions comrising one or more salts or complexes of methyl donors with phytic acid or its derivatives and the method for the synthesis thereof.

Abstract: Provided is a method of treating or preventing age-related macular degeneration (AMD) in a patient subject to, or symptomatic of the disease, wherein the method comprises restoring normal lysosomal pH (pHL), or acidifying an abnormally elevated pHL, thus decreasing or preventing a damaging accumulation of lipofuscin or waste products in the retinal pigment epithelium (RPE) cells of the eye of the patient. Further, this method is achieved by modulating the action of the P2X7 and/or P2Y12 receptors of the RPE cells, specifically decreasing the acidity (pHL) of the RPE lysosomes by administering selected receptor antagonists affecting the action of the P2X7 and/or P2Y12 receptors of the RPE. Methods for selecting and quantifying the effectiveness of drugs to restore pHL and determine outer segment clearance rates is also provided using a high through-put screening protocol.

Abstract: The present invention relates to substituted aminoquinoxaline compounds of general formula (I) in which (II), R2, R3, R4, R6, R7, n and m are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

Abstract: This invention relates to compositions and methods for modulating apoptosis by regulating the activity of endoplasmic reticulum transmembrane glucose regulated protein 78 (GRP78).

Abstract: This invention provides phosphate-modified nucleosides represented by the structural formula (I): wherein W is O or S, and wherein B, R1; R3 and R2. are as defined herein. These compounds are useful as substrates for DNA/RNA polymerases, and as anti-viral agents in particular against HIV-1.

Abstract: A composition comprising a novel Ca2+-activated, [ATP]i-sensitive nonspecific cation (NCCa-ATP) channel is described. The channel is found in mammalian neural cells and exhibits a different sensitivity to block by various adenine nucleotides, and is activated by submicromolar [Ca]i. The NCCa-ATP channel is activated under conditions of ATP depletion, which causes severe cell depolarization, followed by cell swelling. The NCCa-ATP channel is regulated by a sulfonylurea receptor and is inhibited by sulfonylurea compounds glibenclamide and tolbutamide. Methods employing compositions comprising the NCCa-ATP channel to screen for compounds that block the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described. In addition, methods employing compositions comprising the Kir2.3 channel to screen for compounds that open the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described.

Abstract: The present invention relates to 2?-allene-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: The compounds are phosphoramidate derivatives of nucleoside compounds such as cladribine, isocladribine, fludarabine and clofarabine useful in the treatment of cancer.

Abstract: New dietary supplement composition comprising, as active ingredients: NADH and/or NAD+ Coenzyme Q10 Vitamin C (Ascorbic Acid) Serine and/or Phosphoserine to be used for stimulating/improving/increasing the production of naturally occurring adrenaline, thus reducing sleepiness caused by particular drugs intake. The dietary supplement according to the present invention is particularly advantageous for professional drivers and persons who usually take drugs having sleepiness as major side effect.

Abstract: This invention relates to novel phosphate-modified nucleosides, and methods for producing them, being useful for the prevention or treatment of a viral infection in a mammal, and for preparing oligonucleotides by DNA/RNA polymerase-dependent amplification, e.g. PCR.

Abstract: Nutritional compositions and methods of making and using the nutritional compositions are provided. In a general embodiment, the present disclosure provides a nutritional composition including one or more exogenous nucleotides.

Abstract: This disclosure relates to the treatment of hematologic cancers, for example, cancers of the blood, by methods that include administration of EGCG and at least one of a purine nucleoside analog and an alkylating agent. In particular, methods of treating chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL) are described.

Abstract: The present invention discloses methods to identify targets, pathways and molecules regulating purinosomes and their uses for treating pathophysiological disorders associated with purinosomes. Disclosed are methods related to both label-free cellular assays and fluorescence imaging to confirm the regulatory roles of various targets and molecules in purinosome dynamics. Disclosed are methods to classify molecules and the uses of these molecules for different indications. Specifically, the purinosome-disrupting molecules can be used for improved prevention and treatment of cancer development.

Abstract: The present invention relates to a pharmaceutical composition for promoting fertilization comprising cyclic ADP-ribose or its derivative, CD38 and to a method of promoting fertilization by promoting the synthesis of cyclic ADP-ribose to increase sperm motility. Also, the present invention relates to a pharmaceutical composition for contraception and a method for inhibiting fertilization, which can inhibit the expression or function of cyclic ADP-ribose to reduce sperm motility, thereby inhibiting fertilization.

Abstract: The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:

Abstract: The treatment and prevention of thrombotic events are provided through co-administration of PAR-1 and the P2Y12 ADP receptor antagonists. Combined inhibition of the PAR-1 and the P2Y12 ADP platelet activation pathways had synergistic antithrombotic and antiplatelet effects, as demonstrated in co-administration of SCH 602539 and cangrelor.

Abstract: Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

Abstract: Disclosed are nutritional compositions including human milk oligosaccharides and nucleotides that can be administered to preterm infants, term infants, toddlers, and children for reducing inflammation and the incidence of inflammatory diseases.

Abstract: A peritoneal dialysate containing adenosine triphosphate or a salt thereof, and a peritoneal dialysis method using the dialysate. The peritoneal dialysate is safe and causes less peritoneal injuries even when employed in peritoneal dialysis over a long period of time.

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: Disclosed herein are cyclic nucleotide analogs, methods of synthesizing cyclic nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with cyclic nucleotide analogs.

Abstract: Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt or solvate of said compound, isomer or racemic mixture wherein represents an optional double bond, the dotted line is optionally a bond or no bond, resulting in a double bond or a single bond, as permitted by the valency requirement and wherein E, A, G M, Het, B, X, R3, R10, R11, R32 and R33 are herein defined and the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.

Abstract: The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3? ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5? end.

Abstract: A mammal undergoing an energy-based therapy is treated by administering at least one vasoconstrictive agent to the mammal prior to or during the procedure. The at least one vasoconstrictive agent is added in amounts sufficient to reduce or prevent vasodilation. This treatment method increases or promotes the size of the coagulation zone created after energy-based therapy.

Abstract: A process for and intermediates in the preparation of canfosfamide and its salts. Some of the intermediates have anticancer activity.

Abstract: A method for reducing or maintaining platelet inhibition in a patient by administering cangrelor prior to an invasive procedure is described. The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.

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. In some embodiments, the compound is a N6-modified adenosine compound. Methods of screening for and methods of using the compounds are also provided.

Abstract: A method for the treatment of atherosclerosis. The method includes the administration of a 32P-labeled agent as a beta emitter, such as 32P-labeled ATP or other 32P-labeled adenine nucleotides, whereby the 32P-labeled agent seeks and then permeates the atherosclerotic plaque en bloc without prior degradation. The accumulation of the 32P-labeled agent in the atherosclerotic plaque is achieved at time points whereby the 32P-labeled agent is cleared from the blood. Thus, radionuclide-labeled adenine nucleotides accumulate with high specificity in atherosclerotic lesions and in the heart. The beta particles (electrons) emitted by the 32P-label have a maximal path distance of about 0.5 cm and their energy preferentially destroy cells present in the atherosclerotic plaque without affecting vessel integrity or inducing arterial thrombosis.

Abstract: Methods and compositions for treating cancer and other disorders by ?-endorphin therapy are disclosed.

Abstract: The disclosure encompasses caged compounds such as caged nucleoside phosphoesters (caged nucleotides). In an embodiment, the caged nucleotides include compounds corresponding to those described by formula (I) that may be activated by two-photon excitation, and methods of synthesis of such compounds. 8-Bromo-7-hydroxyquinoline-caged ATP was synthesized and examined for its photochemistry as a biologically useful, temporally and spatially controlled ATP-releasing reagent. The combination of two-photon excitation hydrolysis and activation of caged ATP enables methods for finely focusing ATP activation at the sub-cellular level or to a greater depth of activation, thereby providing improved resolution of ATP-dependent processes at the cellular level.

Abstract: The compounds are phosphoramidate derivatives of nucleoside compounds such as cladribine, isocladribine, fludarabine and clofarabine useful in the treatment of cancer.

Abstract: This invention concerns N-(ortho phenylamino dihydropyridyl)sulfonamides and N-(ortho phenylamino dihydropyridyl), N?-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.

Abstract: Disclosed herein are novel phosphonate nucleosides and thiophosphonate nucleosides comprising a phosphonalkoxy-substituted or phosphonothioalkyl-substituted five-membered, saturated or unsaturated, oxygen-containing or sulfur-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

Abstract: Novel cyclic phosphoramidate prodrugs of drugs of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

Abstract: Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

Abstract: This invention provides novel 8-carbyl substituted cAMPS and a novel procedures for the preparation of 8-Br-cAMP, a key starting material.

Abstract: Disclosed herein are phosphoroamidate nucleotide analogs, methods of synthesizing phosphoroamidate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphoroamidate nucleotide analogs.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

Abstract: It has now been found that after administration to a diseased person or person that is at risk for developing such disease of a neutraceutical or pharmaceutical composition that comprises a) a lipid fraction comprising at least one of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA); b) a protein fraction comprising proteinaceous material from non-human origin which provide at least cysteine and/or taurine; and c) a mineral fraction comprising at least one of manganese and molybdenum, the health of these persons improves. Membrane function of several types of mammalian cells improves, which allows efficient treatment of immune related disorders, such as allergy, autoimmune diseases, cancer, cognitive dysfunction and other diseases of the nervous system, neuropathies, such as diabetic neuropathies and neuropathic pains, neuronal damage during insulin resistance, and gut diseases and support of the development of gut and lung function during growth or recovery.

Abstract: The administration of nicotinic acid adenine dinucleotide phosphate (NAADP) or a pharmaceutically acceptable salt thereof to a host in need thereof for the treatment of type-2 diabetes has been disclosed.

Abstract: The invention relates to control of biofilm development. Specifically, some embodiments of the present invention relate to control of bacterial biofilm formation through addition or breakdown of signal(s) that induce biofilm formation. More specifically, some embodiments of the present invention relate to control (e.g., promotion, prevention) of biofilm development by application or hydrolysis of adenosine triphospate (ATP), deoxyadenosine triphosphate (dATP), or derivatives or analogs thereof (e.g., through application or administration of an agent that hydrolyzes ATP, dATP, or derivatives or analogs thereof (e.g., apyrase)).

Abstract: Compounds having the formula I or II, wherein R1, R2, B, and V are as defined herein, are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.