Abstract: Provided herein are novel compounds and novel protected compounds that can be derived from polymyxin, including, e.g., polymyxin A. The novel compounds have antibacterial properties against a diverse range of Gram negative bacteria and reduced toxicity compared to polymyxins such as polymyxin A. Also provided are antibacterial pharmaceutical compositions containing the novel compounds and novel protected compounds, as well as methods for preparing the antibacterial compounds and protected compounds.

Abstract: Provided are prodrugs of pyrrolo[1,2-f][1,2,4]triazin-7-yl nucleoside phosphates wherein the 1? position of the nucleoside sugar is substituted with CN. The compounds, compositions, and methods provided are useful for the treatment Hepatitis C infections.

Abstract: The present disclosure relates to the use and methods of manufacture of bicyclic nucleosides and nucleotides for the treatment and prevention of infectious and proliferative diseases, including microbial infections and cancer.

Abstract: This invention recites isoxazoline substituted azetidine derivatives of Formula (1) stereoisomers thereof, veterinarily acceptable salts thereof, compositions thereof, and their use as a parasiticide in mammals and birds. R1a, R1b, R1c, R2, R3, R4, R6, and n are as described herein.

Abstract: Dermatological conditions/afflictions such as rosacea, common acne, seborrheic dermatitis, perioral dermatitis, acneform rashes, transient acantholytic dermatosis, and acne necrotica miliaris, most notably rosacea, are treated by topically applying onto the affected skin area of an individual in need of such treatment, a topical pharmaceutical composition which comprises a thus effective amount of ivermectin.

Abstract: The present invention relates to compounds which are nystatin derivatives and are anti-fungal agents.

Abstract: A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to a target region within the sequence identified by SEQ ID NO:9, to form a duplex structure between the compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in the cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.

Abstract: A method for treating a patient suffering from multiple sclerosis, particularly a relapsing form of multiple sclerosis, comprising periodically administering a pharmaceutical composition comprising a therapeutically effective amount of OLIGONUCLEOTIDE 1 to the patient, thereby treating the patient.

Abstract: A method of decreasing the expression of LIM kinase 1 in a cancer cell comprising; providing an oligonucleotide consisting of the sequence of SEQ ID NO: 1; providing a cancer cell comprising an mRNA encoding LIM kinase 1; and introducing the oligonucleotide into the cancer cell, wherein the oligonucleotide decreases the expression of LIM kinase 1 in the cancer cell. The method also provides compositions of an antisense RNA LIM kinase 1 that can be administered to an individual for the purpose of inhibiting a protein kinase pathway and which further comprises methods for treating and monitoring the proliferation and metastasis of cancer cells. A kit may be used in the detection and treatment of cancer.

Abstract: The present invention features methods for promoting the differentiation of osteoblast bone forming cells to a mineralization phenotype and increasing bone mass using inhibitors of Brahma. Subjects benefiting from such treatment may have non-union fractures, osteopenia or osteoporosis, osteosarcoma, or a bone graft or bone fusion or orthopedic and dental implants, osteolytic bone disease, skeletal defects or deficiencies or periodontal disease.

Abstract: The invention provides adjuvants, immunogenic compositions, and methods useful for polynucleotide-based vaccination and immune response. In particular, the invention provides an adjuvant of cytofectin:co-lipid mixture wherein cytofectin is GAP-DMORIE.

Abstract: A novel nucleic acid construct for down-regulating angiogenesis in a tissue of a subject is provided. The nucleic acid construct includes: (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain fused to an effector domain of an apoptosis signaling molecule; and (b) a second polynucleotide region encoding a cis acting regulatory element being for directing expression of the chimeric polypeptide in a specific tissue or cell; wherein the ligand binding domain is selected such that it is capable of binding a ligand present in the specific tissue or cell, whereas binding of the ligand to the ligand binding domain activates the effector domain of the apoptosis signaling molecule. Also provided are methods of utilizing this nucleic acid construct for treating diseases characterized by excessive or aberrant neo-vascularization or cell growth.

Abstract: The present invention relates to devices, systems, and methods for improving memory and/or cognitive function by brain delivery of compositions of small interfering RNA or vectors containing the DNA encoding for small interfering RNA. Such compositions can be administered using devices, systems and methods for direct delivery of the compositions to the brain, or using devices, systems, methods of delivery, and compositions that deliver small interfering RNA or vectors containing the DNA encoding the small interfering RNA across the blood-brain barrier. The present invention also provides valuable small interfering RNA vectors, and methods for reduction of BACE1 levels in the hippocampus, cerebral cortex, or other regions of the brain that have beneficial effects on improving memory and/or cognitive function in a subject.

Abstract: The invention is to methods of gene silencing in arthropods using dsRNA. The method is include contacting the arthropod with, and/or directly feeding the arthropod, the dsRNA to the arthropods to deliver the dsRNA to arthropod tissues. It is envisaged that the methods of the invention will have use in determining the biological function of genes in arthropods. Methods of pest control of arthropods, and of protecting arthropods against parasites and predators are provided. Transgenic arthropods expressing dsRNA molecules are also provided by the present invention.

Abstract: A method and composition for treating a host infected with a Caliciviridae virus, such as a Norovirus, comprising administering an effective treatment amount of a described modified nucleoside or a pharmaceutically acceptable salt thereof, is provided.

Abstract: The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2?R)-2?-deoxy-2?-fluoro-2?-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: The present invention relates to reducing accumulation of viral genomes in a target cell. In particular the present invention provides compositions and methods for combating viral infection through RNA interference. Specifically the present invention provides cellular microRNA mimics for treating virus-infected subjects.

Abstract: Heparin-like compounds inhibit collagen-induced platelet aggregation in flowing whole blood. The compounds share properties displayed by native mast-cell derived heparin proteoglycans (HEP-PG) and/or heparin glycosaminoglycan (HEP-GAG) molecules. The compounds are useful in prevention and treatment of severe vascular disorders including arterial thrombosis.

Abstract: A method for targeted delivery of therapeutic compounds from hydrogels is presented. The method involves administering to a cell a hydrogel in which a therapeutic compound is noncovalently bound to heparin.

Abstract: Compositions are provided comprising chito-oligomers obtainable from chitin, comprising oligomers of N-acetyl glucosamine (NAG) and glucosamine, wherein at least 50% of the oligomers have a chain length of about 2-50, and the degree of deacetylation of the oligomers is in the range of about 0-70%, preferably about 30-50%. The compositions are highly useful as pharmaceutical compositions for treatment of joint disorders such as rheumatoid arthritis and osteoarthritis. Also provided are methods for treatment of joint disorders and treatment against inflammatory activity.

Abstract: Methods and compositions involving a class of boron-protected phenylphosphine agents having increased cell permeability and having improved chemical stability for treating or for preventing cell death-related diseases or conditions in a human or a non-human animal.

Abstract: The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders, cancer or rheumatoid arthritis. Processes for preparing these inhibitors are also disclosed.

Abstract: Compositions of submicron- to micron-sized particles of water-insoluble biologically active substances that are stabilized by thermoprotecting agents, can be terminally steam sterilized without any significant increase of mean particle size. These compositions display markedly reduced heat-induced coagulation, flocculation, or particle size growth during the terminal steam sterilization process.

Abstract: The present invention is a solid dosage form of a doxycycline metal complex. The present invention also includes a process for making a doxycycline metal complex in a solid dosage form. The process comprises the steps of (i) providing an aqueous solution of doxycycline or a physiologically acceptable salt thereof; (ii) admixing a metal salt with the aqueous solution; (iii) admixing a base to increase the pH of the aqueous solution, thereby forming a suspension of doxycycline metal; and (iv) drying the suspension, thereby forming a dry granulation of doxycycline metal complex.

Abstract: The present invention provides ascending-dose extended cycle regimens in which a female is administered an estrogen and a progestin for a period of greater than 30 or 31 consecutive days, optionally followed by a hormone-free period or by a period of administration of estrogen. The disclosed regimens can be administered to a female to provide contraceptive and non-contraceptive benefits.

Abstract: The invention relates to novel compounds having the general formula (I), and which compounds are useful to treat a disorder or disease characterized by bronchoconstriction, e.g. COPD and asthma.

Abstract: Method of combating a parasitic protozoal infection of a host organism, wherein the parasite causing the infection is associated with an enzyme system capable of activating tretazicar into a cytotoxic form. The method is carried out by administering tretazicar to the host organism.

Abstract: In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Abstract: The present invention relates to cyclic indolizinecarboxamides and azaindolizinecarboxamides of the formulae Ia and Ib, wherein R, Ra, R10, R20, R30, R40, Y, n, p and q have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they inhibit the enzyme renin and modulate the activity of the renin-angiotensin system, and are useful for the treatment of diseases such as hypertension, for example. The invention furthermore relates to processes for the preparation of the compounds of the formulae Ia and Ib, their use and pharmaceutical compositions comprising them.

Abstract: The present invention provides an improved ibuprofen lysine pharmaceutical composition and a process for preparing the same.

Abstract: The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumors and cancers as well as other disorders or conditions related to or associated with kinases.

Abstract: Pharmaceutical compositions containing a carbapenem of the structural formula I and epicillin are strongly bactericidal against MRSA and MRSE. Equivalently, compositions of conventional carbapenem antibiotics and epicillin are highly synergistic in eradicating said bacteria.

Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents.

Abstract: Disclosed are compounds, compositions and methods for treating diseases, syndromes, conditions and disorders that are affected by the inhibition of MGL, including pain. Such compounds are represented by Formula (I) as follows: wherein Y, r, R2 and Z are defined herein.

Abstract: A composition comprises besifloxacin in an amount effective for treating or controlling an infection caused by an antibiotic-resistant bacterium. Such a composition can be administered to a subject for the treatment or control of bacterial conjunctivitis caused bay an antibiotic-resistant bacterium.

Abstract: The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides benzodiazepine derivatives and methods of using benzodiazepine derivatives as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, and hyperproliferation, and the like.

Abstract: Methods for treatment of depression-related mood disorders in mammals, particularly humans are disclosed. The methods of the invention include administration of compounds capable of enhancing glutamate transporter activity in the brain of mammals suffering from depression. ATP-sensitive K+ channel openers and ?-lactam antibiotics are used to enhance glutamate transport and to treat depression-related mood disorders and depressive symptoms.

Abstract: The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.

Abstract: The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2). The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 and TYK2 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

Abstract: The present invention concerns nitrogenated derivatives of narciclasine and pancratistatin of the following general formula (I) as well their pharmaceutically acceptable salts. The present invention also concerns the use of these compounds in cancer therapy as well as a method for their preparation.

Abstract: The invention provides derivatives of azabicyclo alkane having formula (ID), and the method for making them, wherein each substitute in formula (ID) is same as defined in the description.

Abstract: The present invention relates to compounds of the general formula as dual modulators of the 5-HT2a and D3 receptors useful against CNS disorders, wherein A, R1, R2, n, p, q and r are as defined in the specification.

Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Abstract: The present invention relates to quinoxalinone derivatives of formula (I): wherein R1, R2, R3, R4, R5 and R6 are as defined herein, as insulin secretion stimulators. Specific such quinoxaline compounds are also an aspect of the invention. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated.

Abstract: Compounds of the Formula (I), where W represents CH or N; and Q represents —CN, —C(?NOH)NH2, —CONHR1 or various herein described heterocyclic radicals; as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

Abstract: The present invention relates to inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.

Abstract: The present invention relates to compounds of formula (I) and to pharmaceutically acceptable salts and pharmaceutical compositions thereof. The present invention also relates to use of the compounds of formula (I) in modulating the activity of protein kinases and in the treatment of disease, particularly a disease, disorder or syndrome associated with CDK 4 inhibition.

Abstract: Isoquinolone derivatives of the general formula I are provided. The compounds are NK3 antagonists and useful for the treatment of e.g. psychosis and schizophrenia.

Abstract: Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.