Abstract: The present invention relates to methods of treating bacterial infections and cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula I.

Abstract: Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

Abstract: The present invention relates to particles comprising RNA, in which the RNA is associated with a cationic polymer or lipid or with both a cationic polymer and lipid, wherein the RNA comprises a cytotoxic nucleotide or cytotoxic nucleotide analog and/or the RNA is covalently attached to a cytotoxin, pharmaceutical compositions containing said particles and pharmaceutical uses of the particles and pharmaceutical compositions. The particles of the present invention are particularly useful as an immunostimulating medicament capable to block proliferation or induce death in dividing cells such as tumor cells.

Abstract: Disclosed is a method for synthesizing a novel chiral ligand, a metal chelate, a variety of non-natural amino acids, Maraviroc and a key intermediate thereof. In the invention, (R)-2-methyl proline is selected and used as a starting raw material, (S)-?3-amino acid is obtained by asymmetric resolution induced by using a nickel chelate, and Maraviroc is synthesized by using (S)-3-amino-3-phenylpropionic acid as a key intermediate with a high yield and the ee value reaching 98.2% or more. The method of the present invention has widely available materials, mild synthetic process conditions, is easy to control, and produces a product of a high optical purity.

Abstract: Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

Abstract: In one aspect, the present application relates to an aminothiol-conjugate of formula (I), wherein Core Linker R1, R2, R3, m, n, and p are as described above. The present invention also relates to a method of treating a subject in need of aminothiol therapy using an aminothiol-conjugate of formula (I).

Abstract: Compositions and methods of using nintedanib for improving the success rate of glaucoma filtration surgery are disclosed herein. Nintedanib can be used alone or in combination with an anti-metabolite drug in a topical or implant eye formulation.

Abstract: Aspects of the invention include methods of reducing the deleterious activity of a mutant extended nucleotide repeat (NR) containing target gene in a cell by contacting the cell with an effective amount of a nucleoside agent, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended NR containing target gene may be reduced in a variety of different ways, e.g., by reducing (and in some instances differentially, including selectively, reducing) the production or activity of toxic expression products (e.g., RNA or protein) encoded by the target gene. Kits and compositions for practicing the subject methods are also provided.

Abstract: The present invention relates to methods for the identification of anti-HIV miRNAs and anti-HIV pharmaceutical compounds using high-throughput screening methods, comprising: transfecting reporter cells with a panel of miRNAs, infecting the reporter cells with HIV, screening the cells to identify miRNAs that modulate HIV infection and identifying the specific pathways, nucleic acids and/or polypeptides that are targeted by the miRNAs. The invention further provides for the identification and screening of anti-HIV pharmaceutical compounds having known activity against the specific pathways, nucleic acids and/or polypeptides that are targeted by the miRNAs for efficacy in the treatment of HIV. The invention also provides for the use of miRNA mimics, miRNA inhibitors and pharmaceutical compounds (including oncology drugs and kinase inhibitors) in the treatment and/or prevention of HIV infection.

Abstract: The present disclosure encompasses solid state forms of Sofosbuvir, processes for their production, and pharmaceutical compositions thereof.

Abstract: The invention relates to compositions and methods for utilizing lysophosphatidylcholine scaffolds. The compositions and methods can be used for LPC-mediated delivery of fatty acids and other molecules; to screen and identify fatty acid formulations for parenteral nutrition; and for live animal organ imaging, among other uses. The invention also provides compositions and methods for utilizing mutations and polymorphisms in human Mfsd2a as markers for neurological deficits.

Abstract: 2:1 cocrystals of amino acids and Li+ salts crystallize from hot water to afford water stable cationic networks based upon tetrahedral lithium cations: bilayered square grids, a lithium zeolitic metal-organic material (LiZMOM) and several lithium diamondoid metal-organic materials (LiDMOMs). The compositions may be used as a pharmaceutical for the treatment of suicidality and other disorders that require lithium to penetrate the blood brain barrier and exert therapeutic effects in the CNS. Advantageously, the novel cocrystal forms described herein may be used to lower the oral dose required to achieve therapeutic concentrations of lithium in the brain, thus reducing the peripheral toxicity and potentially broadening the therapeutic index in comparison to conventional lithium forms.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver cancer such as hepatocellular carcinoma, cholangiocarcinoma, or biliary tract cancer. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents. In certain embodiments, the compounds are nucleoside analogs of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, Z1, Z2, Z3, Z4, V, W, X, Ar, R1 and R2 are as described herein.

Abstract: Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

Abstract: Provided herein are methods for inducing cell death in a gram positive bacterium and methods for reducing the proliferation of a gram positive bacterium that include contacting a gram positive bacterium with a dye (e.g., an azo dye) and a TarO inhibitor. Also provided are methods of treating a subject having a gram positive bacterial infection that include administering to a subject having a gram positive bacterial infection a dye (e.g., an azo dye) and a TarO inhibitor. Also provided are compositions containing a dye (e.g., an azo dye) and a TarO inhibitor, and kits containing at least one of these compositions.

Abstract: The present invention relates to anti-cancer compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides analogs of the known anti-cancer compound amonafide, and structurally and functionally related compounds, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with hyperproliferation.

Abstract: Storage stable polyhydroxylated aromatic ether adducts of polyalkylene oxide are described. Reactive compositions are formed by combining an ether adduct with an aldehyde, optionally further adding a phenolic-aldehyde prepolymer. The reactive compositions are cured by removing water, by acidification, or both. The cured compositions sorb solvated compounds from environments containing water. The cured compositions are also useful for pre-loading with compounds that are subsequently released at a controlled rate into environments containing water.

Abstract: Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

Abstract: Disclosed herein are 4?-azido-substituted nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of 4?-azido-substituted 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 4?-azido-substituted nucleoside, a nucleotide and/or an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

Abstract: The present invention relates to the new indications of chronic obstructive pulmonary disease (COPD) and idiophathic lung fibrosis (IPF) for uridine and uridine analogues.

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: Methods for treating tumors comprising cells expressing the vitamin D receptor are provided, and comprise inhibiting the expression or the biologic activity of the vitamin D receptor in the tumor cells, and/or inhibiting the expression or the biologic activity of a constituent of the vitamin D receptor signaling pathway in the tumor cells, and administering to the tumor cells an effective amount of gemcitabine.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Abstract: Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Abstract: Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Abstract: The present invention relates to crystalline complexes of 4-hydroxy benzoic acid and selected pesticides. It also relates to agriculturally useful compositions of the complexes.

Abstract: Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Abstract: Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

Abstract: A method for treating an individual infected with XDR-TB, the method including administering to the individual an anti-XDR-TB drug which comprises a compound having a structure expressed by Structural Formula (1) below:

Abstract: Provided herein are compounds used to inhibit the deamination enzyme responsible for the inactivation of therapeutic compounds, and methods of using them.

Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Abstract: Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, and in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. Antiviral activity of enzyme inhibitors is demonstrated.

Abstract: Methods and compounds are disclosed for irreversibly inhibiting a DNA repair enzyme that possesses lyase activity.

Abstract: The disclosure provides compounds useful as insect repellents, compositions comprising such repellents, and methods of repelling an arthropod using such compounds and compositions. The disclosure further provides insect traps and method for identifying ligands and cognates for biological molecules.

Abstract: This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).

Abstract: Disclosed herein are pharmaceutical compositions that can include a thionucleotide analog for use in combination therapy with other agents. Also disclosed herein are methods of treating diseases and/or conditions with a pharmaceutical composition that can include a thionucleotide analog in combination therapy with other agents.

Abstract: The present invention relates to a method for determining the likelihood of disease outcome of a patient diagnosed with microsatellite stable, stage II colorectal cancer. More in particular, the present invention relates to a method for determining the prognosis of a patient diagnosed with microsatellite stable, stage II colorectal cancer wherein the CpG island methylation status of the promoter of the CHFR gene is determined and wherein methylation of the promoter is indicative of a poor prognosis.

Abstract: The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Abstract: The present invention relates to a pharmaceutical antiretroviral composition comprising lamivudine, festinavir and nevirapine, to a process for preparing such a composition and to the use of such a composition for the treatment and/or prophylaxis of diseases caused by retroviruses, especially acquired immune deficiency syndrome or an HIV infection.

Abstract: Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

Abstract: An agent for treatment of dry eye comprising a combination of a P2Y2 receptor agonist at a therapeutically effective concentration and hyaluronic acid or a salt thereof at a therapeutically effective concentration, which agent has a dosage form of an ophthalmic agent, can promote the secretion of tear remarkably and can improve corneal epithelial disorders remarkably, and is therefore expected to be a novel agent for treatment of dry eye.

Abstract: This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate which inhibits the hepatitis C virus (HCV).

Abstract: Provided herein are methods for inducing cell death in a gram positive bacterium and methods for reducing the proliferation of a gram positive bacterium that include contacting a gram positive bacterium with a dye (e.g., an azo dye) and a TarO inhibitor. Also provided are methods of treating a subject having a gram positive bacterial infection that include administering to a subject having a gram positive bacterial infection a dye (e.g., an azo dye) and a TarO inhibitor. Also provided are compositions containing a dye (e.g., an azo dye) and a TarO inhibitor, and kits containing at least one of these compositions.

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.

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 a composition comprising: (i) one or more of uridine and cytidine, or salts, phosphates, acyl derivatives or esters thereof; and (ii) a lipid fraction comprising at least one of docosahexaenoic acid (22:6; DHA), eicosapentaenoic acid (20:5; EPA) and docosapentaenoic acid (22:5; DPA), or esters thereof, for use in the improvement of the composite NTB score. The invention also provides an improved NTB method comprising an optimized set of individualized tests, in particular for a (prodromal or mild) Alzheimer's or dementia patient.

Abstract: Methods are provided for using methotrexate (MTX) active agents in which reduced host toxicity is observed. Aspects of the methods include administering to a subject an effective amount of an MTX active agent in conjunction with a MTX toxicity-reducing adjuvant, such as a 2,2?-anhydropyrimidine, a derivative thereof or a uridine phosphorylase inhibitor. Also provided are compositions and kits that find use in practicing embodiments of the invention. The methods and compositions find use in a variety of applications, including the treatment of a variety of different disease conditions.