Abstract: Methods of treating exposure to Giardia lamblia and/or giardiasis and methods of antagonizing Giardia lamblia attachment to the intestinal wall of a subject are described herein.

Abstract: The present invention provides a system presenting site-specific accumulation through a ligand that specifically targets a receptor overexpressed on the surface of specific cells within a target organ, like, for example, tumor cells and/or vascular cells of tumor blood vessels. Moreover, this invention provides a method where, upon internalization of the previous-mentioned system by the target cells, triggered release at a high rate of the associated agent takes place, permitting efficient intracellular delivery and, thus, increased concentration of the transported cargo at the target site. Overall, this invention provides a method for the diagnosis, prevention and treatment of human diseases and disorders.

Abstract: Embodiments of the present disclosure include a coordination complex, comprising a first biologically active moiety, a second biologically active moiety, and a metal, wherein the first biologically active moiety and second biologically active moiety are bound to the metal by covalent coordination bonds, and wherein the first biologically active moiety and second biologically active moiety are different. These complexes may enhance the pharmacodynamic properties of biologically active moieties.

Abstract: The present invention is based on the discovery that certain fermentation products of the marine actinomycete strains CNB392 and CNB476 are effective inhibitors of hyperproliferative mammalian cells. The CNB392 and CNB476 strains lie within the family Micromonosporaceae, and the generic epithet Salinospora has been proposed for this obligate marine group. The reaction products produced by this strain are classified as salinosporamides, and are particularly advantageous in treating neoplastic disorders due to their low molecular weight, low IC50 values, high pharmaceutical potency, and selectivity for cancer cells over fungi.

Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of Cannabinoid Receptor 1 (CB1).

Abstract: The invention provides for a method for identifying a biomarker in a fecal sample of a subject in need of such identification comprising: determining whether a fecal sample collected from a subject comprises a biomarker.

Abstract: The invention relates to a method for treating disorders or diseases of a tight junction comprising delivering a pharmaceutical composition of nanoparticles to the tight junction, wherein the nanoparticles consist of positively charged chitosan, a negatively charged substrate, optionally a zero-charge compound, and at least one bioactive agent for treating said disorders or diseases of the tight junction of an animal subject.

Abstract: The present invention provides improved formulations of 6-mercaptopurine that exhibit better bioavailability and faster dissolution than previous formulations.

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: The invention relates to novel compounds for use in the treatment or prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express cytochrome P450 1B1 (CYP1B1) and allelic variants thereof. The invention also provides pharmaceutical compositions comprising one or more such compounds for use in medical therapy, for example in the treatment of prophylaxis of cancers or other proliferative conditions, as well as methods for treating cancers or other conditions in human or non-human animal patients. The invention also provides methods for identifying novel compounds for use in the treatment of prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express CYP1 B1 and allelic variants thereof. The invention also provides a method for determining the efficacy of a compound of the invention in treating cancer.

Abstract: The present invention relates to methods of predicting therapeutic efficacy of thiopurines in an individual by determining the presence of one or more risk variants. In one embodiment, the effective therapeutic efficacy of thiopurines is determined by the presence of risk variants at the genetic loci of HLA-DRB1, CREM, TAGAP, PLCL1, GPX4, SBNO2, MEF2A and/or LYSMD4. In another embodiment, the risk variants are located at the genetic loci of ARL4C, IL1R2, JAK2, 19q13, CARD9, SNAPC4, and/or 8q24. In another embodiment, the individual is has been diagnosed with inflammatory bowel disease.

Abstract: This application concerns certain 2-phenylamino-6-aryl amino-, 6-aryloxy-, and 6-arylthio-purines, -azapurines and -deazapurines. These compounds are non-nucleoside reverse transcriptase inhibitors and have potential as anti-HIV treatment.

Abstract: Compounds and compositions are provided for treatment, prevention, or amelioration of a variety of medical disorders associated with viral infections and/or cell proliferation. The compounds provided herein are 5-phosphono-pent-2-en-1-yl nucleosides and esters thereof.

Abstract: The present invention provides a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof (wherein W represents a hydrogen atom, a halogen atom, or the others; A represents an alkyl group optionally substituted by aryl group or the others, an aryl group, or the others; and one of X and Y represents a di-substituted alkylaminocarbonyl group, or the others, and the other represents a hydrogen atom, an alkyl group, an alkylcarbonyl group, or the others); a medicament or a pharmaceutical composition for treatment or prophylaxis of FAAH-related diseases such as depression, anxiety disorder or pains, comprising the compound or the like as an active ingredient; a use of the compound or the like; and a method for treatment or prophylaxis using the compound or the like.

Abstract: Described herein are novel enzyme inhibitors. In some embodiments, the enzyme inhibitors are reverse transcriptase inhibitors, particularly HIV reverse transcriptase inhibitors. Also described herein are compositions containing them and methods of using them. Thus, the compounds and compositions described herein are useful for the in vitro and in vivo inhibition of HIV reverse transcriptase as a method of treating or preventing HIV, AIDS or related disorders.

Abstract: Described herein are compounds useful in the reduction of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, a compound disclosed herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Abstract: The present invention provides improved formulations of 6-mercaptopurine that exhibit better bioavailability and faster dissolution than previous formulations.

Abstract: The present invention concerns an agent for prevention and treatment of pityriasis. The agent according to the present invention comprises at least one transaminase inhibitor effectively inhibiting the transamination process which is of pathogenetic relevance for the disease, prevents a recurrence of the disease and which protects the human skin flora. Upon release into the environment, no resistances are induced in other fungi.

Abstract: Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein.

Abstract: The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited to, cathepsins and papain-like cysteine proteases. Disease states treated and/or prevented by the compounds of the invention include, but are not limited to, mammalian parasitic diseases in which the parasite utilizes a critical cysteine protease from the papain family. Examples of parasitic diseases to be treated or prevented by the compounds of the invention include, but are not limited to, toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, coccidiosis, giardiosis, cryptosporidiosis or schistosomiasis.

Abstract: A poorly soluble drug containing microsphere with improved bioavailability, an oral formulation comprising the same, and a method of preparing the same are provided, wherein the poorly soluble drug containing microsphere is a solid dispersion wherein the poorly soluble drug is dispersed in the water-soluble polymer carrier in a noncrystalline form by spray drying, thus increasing bioavailability of the poorly soluble drug.

Abstract: This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

Abstract: This application provides compositions and methods useful in the treatment of certain cancers. In part, this application is based on the recognition that certain molecules that target abasic lesions or AP sites in DNA improve, augment, or potentiate the chemotherapeutic efficacy of certain anticancer agents.

Abstract: Disclosed herein is a method of promoting neuronal outgrowth in a neuron. The method comprises contacting the neuron with an effective amount of hypoxanthine, to thereby promote neuronal outgrowth of the neuron. The hypoxanthine may be contacted in the absence of xanthine oxidase and/or in the absence of exogenous nerve growth factor (NGF), and/or in the absence of exogenous D-mannose, and/or in the absence of exogenous oncomodulin, and/or in the absence of exogenous TGF-B. The neuron may be an optic nerve neuron or a retinal neuron and/or an injured neuron. Neurons may be from the central nervous system (CNS) or the peripheral nervous system (PNS). The methods are useful for treating an injured neuron, for example to an optic nerve neuron, resulting from branch and central vein/artery occlusion, trauma, edema, angle-closure glaucoma, open-angle glaucoma. Methods of treatment of various neurological injuries and diseases, as well as therapeutic compositions, are also disclosed.

Abstract: The invention provides nanostructures or products of manufacture for use as ex vivo or in vivo composition (e.g., a drug, or a therapeutic, diagnostic or imaging reagent) delivery vehicles. In one aspect, the invention provides nanoparticles comprising several compartments which in unison function as a composite nanostructure. In one embodiment, the nanoparticles of the invention comprise a combination of polymer core/lipid bilayer interface which incorporate covalently attached lipid-vascular targeting ligands. These composite nanoparticles can deliver highly effective and selective payloads for diagnostic, prophylactic or therapeutic applications.

Abstract: Disclosed is a sustained release system that includes a polymer and a prodrug having a solubility less than about 1 mg/ml dispersed in the polymer. Advantageously, the polymer is permeable to the prodrug and may be non-release rate limiting with respect to the rate of release of the prodrug from the polymer. This permits improved drug delivery within a body in the vicinity of a surgery via sustained release rate kinetics over a prolonged period of time, while not requiring complicated manufacturing processes.

Abstract: The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.

Abstract: The invention relates to a controlled release pharmaceutical composition, comprising a core, comprising a pharmaceutical active ingredient, whereby the core is coated by an ethanol resistance conferring coating layer which has the effect of conferring the release profile of the pharmaceutical active ingredient to be resistant against the influence of ethanol. The coating layer comprises a polymeric portion consisting of a water-insoluble neutral vinyl polymer or vinyl copolymer and an amino methacrylate copolymer and an excipients portion consisting of a lubricant, an emulsifier, a plasticizer and optionally a cellulosic compound.

Abstract: In one aspect, the invention relates to a method for identifying a drug candidate with activity as a neuroprotective agent. The method includes determining whether a compound reduces ATF4 activity; and identifying the compound that reduces ATF4 activity as a drug candidate.

Abstract: The present invention is directed to a method of treating systemic lupus erythematosus comprising administering a compound of formula (I) wherein R1 is selected from the group consisting of CF3, a C1-C5 alkyl, and (CH2)nR4, wherein n is between 0 and 4; R2 is selected from the group consisting of (CH2)mR4 and (CH2)mAr, wherein m is between 0 and 5; R3 is selected from the group consisting of hydrogen and methyl; R4 is selected from the group consisting of phenyl, OH, a C1-C3 alkoxy, a C1-C3 dialkylamino, piperidino, and N-methylpiperazino; Ar represents ?wherein X is selected from the group consisting of F, C1, a C1-C3 alkoxy, and CF3. The compounds can be used in combination with a second compound used in the treatment of systemic lupus erythematosus.

Abstract: The present invention relates to conjugates of a drug and an amino acid or an amino acid derivative or analog, pharmaceutical compositions that include the conjugates and methods of use thereof. In particular, the present invention relates to conjugates of anti-proliferative drugs and asparagine and glutamine and analogs thereof as compositions for treatment of cancer, and conjugates of imaging agent carriers and amino acids for the diagnosis of tumors and metastases.

Abstract: This invention relates to novel (6-phenyl-5-amino/nitro-pyrimidin-4-yl)-phenyl-amines, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Abstract: 8-quinolinol (8Q) and derivatives thereof for use in the treatment of proliferative diseases such as cancer, in particular slow metabolizing quiescent cancer stem cells.

Abstract: The present invention is directed toward a method of treating a subject for a condition mediated by aberrant Wnt/?-catenin signaling by selecting a subject with a condition mediated by aberrant Wnt/?-catenin signaling and administering to the selected subject at least one compound selected from the group consisting of those set forth in Table 1, Table 2, Table 3, and a pharmaceutically acceptable salt thereof. A method of similarly modulating the Wnt/?-catenin pathway in a subject is also discussed.

Abstract: Provided herein are Heteroaryl Compounds having the following structure: wherein R1, R3, R4, L, X, Y, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.

Abstract: This invention provides a method of treating a subject afflicted with active lupus arthritis comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the subject. This invention also provides laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with active lupus arthritis. This invention further provides a pharmaceutical composition comprising an amount of laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with lupus arthritis.

Abstract: 2-Phenoxy pyrimidinone analogues are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

Abstract: The present invention relates to new quinoline inhibitors of tyrosine kinases, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Compositions and methods for modulating HSP70 function, particularly for the targeted killing of cancer cells, are disclosed.

Abstract: The invention relates to compounds and methods for treating or preventing a viral infection, by administering a monophosphorylated prodrug of acyclovir or monophosphorylated derivative of an acyclovir prodrug to a subject suffering from or susceptible (to a viral infection, such as HIV infection.

Abstract: A compound for modulating kinase activity according to Formula I, or a pharmaceutically acceptable salt thereof, Wherein J1, J2, J3, R2, J4, Z, Ar and R3 are as defined in the specification, compositions thereof, and methods of use thereof.

Abstract: The invention relates to immunotherapeutic compounds and to methods for stimulating an immune response in a subject individual at risk for developing cancer, diagnosed with a cancer, in treatment for cancer, or in post-therapy recovery from cancer or the compounds of the invention can be administered as a prophylactic to a subject individual to prevent or delay the development of cancer.

Abstract: Disclosed are compounds and compositions that inhibit the action of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), methods of inhibiting FAAH and MGL, methods of modulating cannabinoid receptors, and methods of treating various disorders related to modulation of cannabinoid receptors.

Abstract: Provided herein are Heteroaryl Compounds having the following structure: wherein R1, R3, R4, L, X, Y, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.

Abstract: It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies.

Abstract: The present invention provides systems for developing and/or testing therapies for prenatal diseases and conditions including Down Syndrome. The present invention also provides diagnostic methods for Down Syndrome involving, in some embodiments, gene expression analyses of fetal RNA and/or detection of expression of particular genes involved in Down Syndrome. Also provided are microarrays and kits useful in prenatal diagnostic applications.

Abstract: A method for determining a therapeutically effective amount of suramin for administering to a patient, who is to receive a cytotoxic agent, which comprises the steps of determining the circulating suramin concentration in the patient; administering suramin, if required, to establish a low circulating concentration of suramin in the patient of below about 200 ?M; and administering the chemotherapeutic agent to the patient when the low circulating concentration of suramin is present in the patient. Conveniently a nomogram can be constructed for use in clinical settings with the suramin.

Abstract: A compound of general Formula (I) having histone deacetylase (HDAC) and/or CDK inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.

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: Novel methods of treating proliferative disorders characterized by elevated Her-2, and the patient is then administered an effective amount of an HSP90 inhibitor.