Abstract: The present invention provides assay methods for identifying agents that affect a secretory pathway in an invertebrate pest cell. The methods are useful for identifying agents that modulate a secretory pathway in an invertebrate pest cell, and that are therefore useful as pesticidal agents. The invention further provides methods for identifying secretory pathway proteins in an invertebrate pest cell, which secretory pathway proteins serve as targets for pesticides. The method further provides pesticidal agents identified using the assay methods of the instant invention.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided.

Abstract: Use of compounds modulating P2 purinoceptors, in particular antagonists such as Basilen Blue E-3G (Reactive Blue 2), for the prevention of the damages due to global cerebral ischemia and ischemia-reperfusion. Said compounds reduce the mortality in case of global cerebral ischemia as well as the neuronal damage of the hippocampus.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of daxx. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding daxx. Methods of using these compounds for modulation of daxx expression and for treatment of diseases associated with expression of daxx are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of short heterodimer partner-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding short heterodimer partner-1. Methods of using these compounds for modulation of short heterodimer partner-1 expression and for treatment of diseases associated with expression of short heterodimer partner-1 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of p70 S6 kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding p70 S6 kinase. Methods of using these compounds for modulation of p70 S6 kinase expression and for treatment of diseases associated with expression of p70 S6 kinase are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of PKA regulatory subunit RII beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PKA regulatory subunit RII beta. Methods of using these compounds for modulation of PKA regulatory subunit RII beta expression and for treatment of diseases associated with expression of PKA regulatory subunit RII beta are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of RECQL5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding RECQL5. Methods of using these compounds for modulation of RECQL5 expression and for treatment of diseases associated with expression of RECQL5 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of C-reactive protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C-reactive protein. Methods of using these compounds for modulation of C-reactive protein expression and for treatment of diseases associated with expression of C-reactive protein are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of stearoyl-CoA desaturase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding stearoyl-CoA desaturase. Methods of using these compounds for modulation of stearoyl-CoA desaturase expression and for treatment of diseases associated with expression of stearoyl-CoA desaturase are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of transforming growth factor-beta 3. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding transforming growth factor-beta 3. Methods of using these compounds for modulation of transforming growth factor-beta 3 expression and for treatment of diseases associated with expression of transforming growth factor-beta 3 are provided.

Abstract: Disclosed are compounds of the formula (I) wherein: R2, R7, RI3, R14 and R15 are independently hydrogen, or (un)substituted lower alkyl, (un)substitued lower alkenyl, (un)substituted lower alkynyl, or (un)substituted —(CH2)nR12; R5 is halogen, cyano, nitro, —R9, —NR9R10, or —OR9; R6 is halogen, cyano, nitro, —R9, —NR9R10, —OR9, —Co2R9, —COR9, —CONR9R10, —NR9COR10, (un)substiuted lower alkenyl, or (un)substituted lower alkynyl; R8 is —CO2R13, —COR13, —CONR13R14, —CSNR13R14, —C(NR13)NR14R15, —SO3R13, —SO2R13, —SO2NR13R14, —PO3R13R14, —POR13R14, —PO(NR13R14)2; R9 and R10 are independently hydrogen or (un)substituted lower alkyl; R11 is a heteroaryl or a heterocyclic group; R12 is a cycloalkyl, a heterocyclic, an aryl, or a heteroaryl group; and n is 0,1,2, or 3.

Abstract: The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPase's) such as PTP1B, CD45, SHP-1, SHP-2, PTP&agr;, LAR and HePTP or the like.

Abstract: Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy.

Abstract: The present invention provides selenium derivatives of nucleosides, nucleoside phosphoramidites, nucleotides, nucleotide triphosphates, oligonucleotides, polynucleotides, and larger nucleic acids and methods for their synthesis. Selenium derivatives of both ribonucleic acids and deoxyribonulcleic acids, as well as methods for their synthesis, crystallization and uses in structural determinations, particularly by X-ray crystallographic techniques are disclosed. The selenium derivatives of the present invention are also useful as food supplements.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Inhibitor-kappa B Kinase-beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Inhibitor-kappa B Kinase-beta. Methods of using these compounds for modulation of Inhibitor-kappa B Kinase-beta expression and for treatment of diseases associated with expression of Inhibitor-kappa B Kinase-beta are provided.

Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.

Abstract: The present invention relates to (1R, cis)-4-(4-Amino-7H-pyrrolo[2,3-(d)]pyrimidine-7-yl)-2-cyclopentene-1-methanol derivatives for the treatment of viral infections.

Abstract: Inosine compounds, compositions comprising an inosine compound and methods for treating or preventing an inflammation disease or a reperfusion disease comprising administering an effective amount of an inosine compound to a patient in need thereof are disclosed.

Abstract: The present invention relates to analogs of (1S, cis)-4-(2-amino-9H-purin-9-yl)-2-cyclopentene-1-methanol for use in treating viral infections.

Abstract: Methods for delivering ligands to a cell by using light to activate fluorescent ligands causing their release from endosomes. The instant methods thus increasing the efficiency of ligands, e.g. in vitro or at localized sites within a subject. The invention provides for the release of ligands by shining a light source on a cell to promote release of ligands into the cell where they can effect their function.

Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating or preventing conditions, including hyperproliferative conditions, associated with raf expression.

Abstract: The present invention is directed to a method of altering the amount or composition of synovial fluids secreted from joints in a subject in need of such treatment. The method comprises administering to a subject a pharmaceutical composition comprising a P2Y purinergic receptor agonist in an amount effective to alter the amount or composition of synovial fluids. The P2Y purinergic receptor agonist is administered in an amount effective to stimulate secretion of synovial fluid, lubricin, hyaluronic acid, or surface-active phospholipids; to enhance joint lubrication; or to treat osteoarthritis. The pharmaceutical compositions useful in the present invention comprise a P2Y purinergic receptor agonist of Formula I and include, but are not limited to: uridine-, adenosine-, cytidine-5′-di- or triphosphates, dinucleoside polyphosphates, and analogs thereof. The invention is useful for treating conditions associated with reduced joint lubrication and joint stiffness, such as osteoarthritis.

Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Abstract: Several lines of evidence have shown a role for the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cGMP are not fully understood in the processing of pain in the spinal cord. cGMP-dependent protein kinase (PKG) I&agr; but not PKGI&bgr; was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of an inhibitor of PKGI&agr;, Rp-8-[(4-Chlorophenyl)thio]-cGMPS triethylamine, produces significant antinociception. Moreover, PKGI&agr; protein expression was dramatically increased in the lumbar spinal cord after noxious stimulation. This upregulation of PKGI&agr; expression was completely blocked not only by a neuronal NO synthase inhibitor, and a soluble guanylate cyclase inhibitor, but also by an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801.

Abstract: The present invention relates to novel compounds, compositions and methods for inhibiting the growth, elaboration and/or replication of HIV in human patients and to the prevention and treatment of human acquired immunodeficiency syndrome (AIDS) and other diseases caused by retroviral infection. More particularly, in preferred aspects, the present invention provides a method for the use of novel prodrug forms of 9-(2,3-Dideoxy-&bgr;-D-glycero-pent-2-enofuranosyl)guanine (d4G) for the prevention and treatment of both wild type and drug-resistant Human Immunodeficiency Virus (HIV), the causative pathogen of AIDS.

Abstract: The present invention provides methods and compositions for slowing the transit time of pharmaceutical compounds, nutritional supplements, and vitamins through the gastrointestinal tract, prolonging residence time of such compounds, and thereby increasing absorption in the small intestine, by utilizing the cellular regulatory compound cyclic GMP. The present invention also provides methods and compositions for enhancing the bioavailability and therapeutic effectiveness of pharmacologically active agents, vitamins, and nutritional supplements.

Abstract: Dioxolane analogs of the following formula: 1

Abstract: The present invention relates to glycoconjugates of 20(S)-camptothecin, in which a 3-O-methylated &bgr;-L-fucose unit is linked to the 20-hydroxyl group of a camptothecin derivative via a thiourea-modified peptide spacer. The invention furthermore relates to processes for the preparation of the compounds according to the invention and to their use as medicaments, in particular in connection with oncoses.

Abstract: A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer.

Abstract: The invention provides a compound of formula (I): 1

Abstract: Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

Abstract: A compound of formula (I) which is an agonist at the adenosine Al receptor, wherein Y, Z, and W represent heteroatoms, and salts and solvates thereof, in particular, physiologically acceptable solvates and salts thereof for use in therapy.

Abstract: The present invention relates to glycoconjugates of camptothecin derivatives in which at least one carbohydrate component is linked via suitable spacers with the 20-hydroxyl group of a camptothecin derivative. The invention furthermore relates to processes for preparing the compounds according to the invention and to their use as medicaments, in particular in connection with cancer.

Abstract: It has been unexpectedly found that a drug resistant strain of HIV exhibits the behavior of drug-naïve virus when given the combination of a &bgr;-D-1,3-dioxolanyl nucleoside and an IMPDH inhibitor. In one nonlimiting embodiment, the HIV strain is resistant to a &bgr;-D-1,3-dioxolanyl nucleoside.

Abstract: Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-&agr; and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-&agr;) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.

Abstract: The invention provides a method and compositions for controlling food borne enteric bacterial pathogens in animals. Populations of enteropathogenic bacteria may be substantially reduced or eliminated by treatment of animals with an effective amount of the compound Xm(ClO3)n, wherein X is a cationic moiety and m and n are independently selected from integers necessary to provide a net valency of 0. The compounds may be administered orally, providing a reduction in the populations of the enteropathogenic bacteria in the alimentary tract of the animal, or they may be applied externally onto the animal to reduce the populations of any such bacteria which may be present as contaminants on the surface of the animal. The method and compositions are particularly useful for the control of Salmonella species, enteropathogenic Escherichia coli, and Clostridia species.

Abstract: Several lines of evidence have shown a role for the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cGMP are not fully understood in the processing of pain in the spinal cord. cGMP-dependent protein kinase (PKG) I&agr; but not PKGI&bgr; was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of an inhibitor of PKGI&agr;, Rp-8-[(4-Chlorophenyl)thio]-cGMPS triethylamine, produces significant antinociception. Moreover, PKGI&agr; protein expression was dramatically increased in the lumbar spinal cord after noxious stimulation. This upregulation of PKGI&agr; expression was completely blocked not only by a neuronal NO synthase inhibitor, and a soluble guanylate cyclase inhibitor, but also by an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801.

Abstract: The present invention relates generally to oligonucleotide analogues that include novel protein nucleic acid molecules (PNAs), particularly monomers, dimers, oligomers thereof and methods of making and using these oligonucleotide analogues. The PNAs of the present invention are characterized as including a variety of classes of molecules, such as, for example, hydroxyproline peptide nucleic acids (HypNA), and serine peptide nucleic acids (SerNA). The invention includes monomers, homodimers, heterodimers, homopolymers and heteropolymers of these and other oligonucleotide analogues. The present invention includes methods of using these oligonucleotide analogues in the detection and separating of nucleic acid molecules, including uses that include the utilization of oligonucleotide analogues on a solid support. The present invention also includes methods for purifying or separating nucleic acids, such as mRNA molecules, by hybridization with the oligonucleotides of the present invention.

Abstract: The present invention provides methods for treating rhinoviral infections in a subject in need of such treatment, by the administration of 2′-5′ oligoadenylates or the analogs thereof. Pharmaceutical formulations comprising 2′-5′ oligoadenylates and analogs thereof are also provided.

Abstract: A method and associated compounds for forming nanotubes are disclosed.

Abstract: Nucleozymes containing ribonucleotides and deoxyribonucleotides or nucleic acid analogues are described herein. The nucleozymes have catalytic activity and are significantly more resistant to degradation than their all-RNA ribozyme counterparts. Also described are methods for preparing the nucleozymes along with methods of using nucleozymes, e.g., as therapeutic agents.

Abstract: Aryl substituted phosphoryl derivatives of the formula In which Ar is phenyl, naphthyl, or pyridyl, Y is O or S, X1 is O, NR3, S, CR3R4, CR3W1 or CW1W2, X2 and X6 are a bond or X6 is CH2 and X2 is O, NR3, S, CR3R4, CR3W1 or CW1W2, R3 and R4 are H, alkyl or phenyl, groups, W1 and W2 are heteroatoms, X3 is alkylene, X4 is oxygen or CH2, X5 is a bond or CH2, Z is O, NR5, S, alkyl or phenyl, R5 is H, alkyl or phenyl, J is H, alkyl, phenyl, or a heterocyclic or polycyclic group, Q is O, NR6, S, CR6R7, CR6W3 or CW3W4, R6 and R7 are H, alkyl, or phenyl, and W3 and W4 are hetero atoms, T1 and T2 are H or CH2R8, R8 is H, OH or F, or T1 and T2 together are —CH═CH— or —C(R9)(R10)C(R11)(R12)—, R9 is H, halogeno, CN, NH2, CO-alkyl, or alkyl, R10, R11, and R12 are H, N3, halogen, CN, NH2, CO-alkyl, or alkyl, and B is a purine or pyrimidine base, have antiviral activity, as for example against HIV.

Abstract: The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.

Abstract: This invention provides a novel class of substituted macrocyclic metallic complexes. The complexes are useful as peroxynitrite decomposition catalysts. Pharmaceutical compositions, and methods of making and using the compounds, or a pharmaceutically acceptable salt, hydrate, prodrug, or mixture thereof are also described.

Abstract: The present invention relates to a novel nucleotide analogue having the general formula (I) and pharmaceutically acceptable salts, esters, or salt of such esters: wherein n, X, Q U R1′, R1, Z and R2 are defined here within. The compounds object of the present invention may be a single enantiomers or as mixtures of said enantiomers, the compounds may have a &agr;D, &agr;-L, &bgr;-D, &bgr;-L, R or S configuration at each chiral center or mixtures thereof. This invention also relates to pharmaceutical compositions containing them, alone or in combination with other therapeutic agents, and their use as antiviral agents, particularly against HIV and/or HBV infections in mammals.

Abstract: Compositions of matter having protein kinase C-modulatory, anti-inflammatory and other biological activities are disclosed. The compositions are derived from indolactams which have a substituent, containing at least one carbon, at the N1 position and have ether substitution on the 14-O position.

Abstract: The present invention relates to certain novel dinucleotide polyphosphates of general Formulae I, II and III, and formulations thereof which are selective agonists of the P2Y purinergic receptors. They are useful in the prevention, management or treatment of diseases and disorders associated with abnormalities of tissue fluid secretion, hydration and clearance, including chronic obstructive pulmonary diseases (chronic bronchitis, PCD, cystic fibrosis, immobility-associated pneumonia), sinusitis, otitis media, nasolacrimal duct obstruction, dry eye disease, glaucoma, retinal degeneration, and edematous retinal disorders, including retinal detachment, vaginal dryness, and gastrointestinal tract disease. Finally, these novel dinucleotides may be useful for diagnostic purposes, such as the facilitation of sputum induction and expectoration for the analysis of respiratory tract secretions.

Abstract: Nucleosides and other compounds to selectively modulate Th1 and Th2 responses relative to each other in the treatment of disease. In one aspect of the invention, administration of a nucleoside or other compound reduces the dosage at which a primary drug is administered. In another aspect of the invention, an abnormality reflected in increased response in one group of cytokines is treated by administering a nucleoside or other compound that increases response in another group of cytokines. In yet another aspect of the invention, a patient is prophylactically treated by administering a nucleoside or other compound that selectively reduces Th1 activity without significantly reducing Th2 activity. In yet another aspect of the invention, a nucleoside or other compound is administered to a patient at a dose that reduces the patient's GTP pool to a degree that selectively reduces one of the Th1 or Th2 responses without significantly reducing the other response.