Abstract: The present disclosure relates to methods of treating a patient suffering from or at risk of developing an ocular disease, disorder or injury, and includes treatment regimens using a double-stranded RNA compound that down-regulates CASP2 expression, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to the use of substituted dihydroimidazolones, particularly [1-(4-Chlorophenyl)-4-(4-morpholinyl)-2,5-dihydro-1H-imidazol-2-one] (AWD 131-138) or a physiologically acceptable salt thereof for the treatment of epilepsy in dogs.

Abstract: The invention provides tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist. The invention further provides solid compositions comprising tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist. The invention further provides uses of tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist, e.g., for treating type 1 diabetes, type 2 diabetes, or obesity.

Abstract: The present invention provides methods of use of oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and wherein said methods of use include uses for the treatment of disorders and diseases, such as diabetes.

Abstract: The present invention relates to the field of therapeutic methods to screen for compounds on the basis of their ability to influence Wnt activity. The screening process is applied to both a physical library of a series of compounds and a virtual library of compounds that affect Wnt activity. In one aspect, the virtual screening process could be carried out where a permutational library of small peptides is substituted for the small organic molecules. The inventive methods may be used to empirically test for effects on Wnt activity and may also be applied to any pair of proteins involved in protein-protein interactions.

Abstract: Disclosed is a stable formulation based on rAFP conjugated with drug delivery system of various classes of pharmacological agents such as dactinomycin, cardionolide, and bufadinolide, among others. In another embodiment, the invention discloses a method of producing rAFP in a strain of methylotrophic Pichia pastoris yeast, allowing the yeast to replicate, and extracting the newly created rAFP. The method provides a nonpyrogenic, highly stable, recombinant, fully refolded rAFP and its fragments that are free from stable folding intermediates caused by non-native disulfide bridges and irreversible aggregates. The newly created rAFP is purified using a two-step chromatographic purification process in the presence of 0.5% polysorbate-20 and 10 mM inosine that prevents aggregation of the monomers of the target protein, increasing the yield of biologically active rAFP.

Abstract: The present invention relates to methods for treating an infectious disease in a subject in need thereof via administration of a therapeutically effective amount of compounds described herein. The methods may utilize particular compounds, for example, a quinoline, a hydrazone, a quinone, or a pyrimidine derivatives thereof or a pharmaceutical salts thereof.

Abstract: The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and/or reducing the risk of microbial infections in humans and animals.

Abstract: The present invention provides methods of use of oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and wherein said methods of use include uses for the treatment of disorders and diseases, such as diabetes.

Abstract: Pharmaceutical compositions for treating Alzheimer's disease are disclosed. The pharmaceutical compositions include a compound having the general formula: and a pharmaceutically acceptable carrier. Methods for treating Alzheimer's disease, inhibiting ATase I and/or ATase 2, reducing the activity of BACE1, reducing the level of amyloid ?-peptide (A?), and/or reducing the level of APP intracellular domain peptide (AICD) by administering such compositions are also disclosed.

Abstract: The present invention relates to antibacterial compounds of formula I: wherein all variable substituents are defined as described herein, which are useful for the treatment of bacterial infections.

Abstract: The present disclosure is directed to methods of identifying a compound that binds to or interacts with a protein receptor involved in bone formation. Specifically, the disclosure is directed to methods of identifying a compound that regulates a Wnt pathway in a cell by binding to or interacting with cavities in proteins such as LRP5, LRP 6 and/or frizzled receptor and interfering with receptor binding to other proteins in a Wnt pathway. The present disclosure is further directed to methods and compositions that comprise an identified compound for treating or preventing a disease in a mammal in which Wnt pathway suppression plays a role.

Abstract: The present invention relates to the use of substituted dihydroimidazolones, particularly [1-(4-Chlorophenyl)-4-(4-morpholinyl)-2,5-dihydro-1H-imidazol-2-one] (AWD 131-138) or a physiologically acceptable salt thereof for the treatment of epilepsy in dogs.

Abstract: The present invention provides methods of synthesizing oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and methods of synthesizing precursors to these oxadiazoanthracene derivatives.

Abstract: A process for the characterization of rosacea is disclosed. The process can include identifying for the first time new markers in leukocyte recruitment as well as the therapeutic applications targeting rosacea.

Abstract: Compositions of matter including (R)-2,5,6,8-tetramethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine and (R)-2,6,8-trimethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine are disclosed herein. Further disclosed are methods of preparation of such compounds and the use of such compounds as anticancer agents.

Abstract: The present invention provides protein (or peptide)-polysaccharide (or oligosaccharide) conjugates (PPC) as nanocapsular vehicles for nanoencapsulation of biologically active compounds, particularly nutraceuticals. The PPCs efficiently protect both hydrophobic (i.e., water insoluble) and hydrophilic (i.e., water soluble) nutraceuticals, to provide a composition which, when added to a beverage, disperses so as to provide a clear or transparent solution. In some embodiments, the PPCs are Maillard reaction based PPCs. Advantageously, the conjugates of the present invention protect the nutraceuticals from degradation, both during shelf life and upon gastric digestion.

Abstract: The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, malaria, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; killing or inhibiting the growth of a Plasmodium species; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative.

Abstract: The claimed invention is directed to compositions and methods effective in preventing microbial contamination or reducing microbial count associated with a contaminated surface, comprising a biocidal system comprised of a primary biocide, a pH buffer agent, a surfactant, all in an aqueous based carrier, wherein the compositions may be considered environmentally friendly.

Abstract: The present invention relates to the use of substituted dihydroimidazolones, particularly [1-(4-Chlorophenyl)-4-(4-morpholinyl)-2,5-dihydro-1H-imidazol-2-one] (AWD 131-138) or a physiologically acceptable salt thereof for the treatment of epilepsy in dogs.

Abstract: The present disclosure relates to 2,4-pyrimidinediamines substituted with tricyclic carbamates and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, such as JAK2 or JAK3, is therapeutically useful.

Abstract: Compounds of Formula I: (wherein variables A1, A2, A3, ring-B, m, n, J, E1, E2, E3, R5, RPG and Y are as described herein), which are useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising the compounds of formula (I) and the use of these compounds and compositions in the prevention or treatment of diseases in which CGRP receptors are involved.

Abstract: Disclosed herein are resorufin derivative compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging.

Abstract: Compositions of matter including (R)-2,5,6,8-tetramethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine and (R)-2,6,8-trimethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine are disclosed herein. Further disclosed are methods of preparation of such compounds and the use of such compounds as anticancer agents.

Abstract: Aspects of the present invention provide compositions comprising a sulfur containing compound and a compound of the formula (I); and also provide methods of their preparation and use.

Abstract: Disclosed herein are maytansinoid drug linker derivatives which can be linked to a antigen binding unit (Abu), and maytansinoid drugs linked with an antigen binding unit (Drug-Linker-Antigen binding Unit: D-L-Abu), for targeted delivery to disease tissues. D-L-Abu, D-L-Abu derivatives, and methods relating to the use of such drug conjugates to treat antigen positive cells in cancers and immunological disorders are provided.

Abstract: The present invention relates to the C-13 molecule (methyl 2-{5-[(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}-benzoate) and to organic molecules functionally equivalent to the C-13 molecule, capable of inhibiting the binding of an antibody or antibody fragment with the human Syk protein tyrosine kinase, to the use of these molecules for the production of medicaments for the prevention or treatment of diseases dependent on metabolic pathways involving Syk, and also to a method for identifying such molecules.

Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.

Abstract: Piperidinodihydrothienopyrimidines of formula 1 wherein X is SO or SO2 (preferably SO), and R1, R2, R3, and R4 may have the meanings given in the disclosure and claims, pharmacologically acceptable salts thereof, and pharmaceutical compositions containing these compounds. These piperidinodihydrothienopyrimidines are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system, or cancers.

Abstract: Described are a compound of formula (II) or (III): The compounds are effective in the treatment of disease, including a tauopathy condition or a disease of tau protein aggregation.

Abstract: This invention relates, e.g., to a method for designing or selecting on a computer a candidate small molecule amyloid binder or inhibitor, comprising: a) docking test compounds to the binding site or binding surface determined from the three-dimensional structure of a co-crystal of a protofilament of an amyloid protein bound to a small molecule which is known to bind to the amyloid protein, and (b) selecting test compounds which exhibit an energy below that of the small molecule used to form the co-crystal made in a), as candidate amyloid binders.

Abstract: The present invention provides methods of use of oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and wherein said methods of use include uses for the treatment of disorders and diseases, such as diabetes.

Abstract: The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 that is required for the coreceptors' transport to cell surfaces, resulting in less LRP5 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm.

Abstract: The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

Abstract: The present invention provides methods and compositions for treating or preventing viral infections using modulators of host cell enzymes relating to mTOR. The invention also provides methods and compositions for treating or preventing viral infections using modulators of host cell enzymes relating to mTOR and modulators of the unfolded protein response.

Abstract: The present invention relates to tricyclic compounds, and pharmaceutical compositions of the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer.

Abstract: The present invention provides methods of use of oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and wherein said methods of use include uses for the treatment of disorders and diseases, such as diabetes.

Abstract: Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as ?-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease.

Abstract: The invention provides novel pharmaceutical compositions based on semifluorinated alkanes which are useful as carriers for a broad range of active ingredients. Preferred active ingredients include poorly water-soluble and/or hydrolytically sensitive drug substances. The compositions are designed as suspensions and have superior physical properties which make them highly useful as pharmaceutical delivery systems. The compositions may be administered topically into the eye, or injected via the subcutaneous or intramuscular route. The invention further provides kits comprising such compositions.

Abstract: The invention relates to a series of compounds with particular activity as inhibitors of the serine-threonine kinase AKT. Also provided are pharmaceutical compositions comprising same as well as methods for treating cancer.

Abstract: The present invention provides methods of use of oxadiazoanthracene derivatives of the formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, R, R1, R2, R3, R4 and R5 are as herein described, and wherein said methods of use include uses for the treatment and/or prevention of disorders and diseases, such as diabetes.

Abstract: Effective treatments of pain for extended periods of time are provided. Through the administration of an effective amount of mixed monoamine reuptake inhibitor locally at or near a target site, one can relieve pain caused by diverse sources, including but not limited to spinal disc herniation (i.e. sciatica), spondilothesis, stenosis, discogenic back pain and joint pain, as well as pain that is incidental to surgery. When appropriate formulations are provided within biodegradable polymers, this relief can be continued for at least thirty days. In some embodiments, the relief can be for at least at least fifty days, at least one hundred days, at least one hundred and twenty days, at least one hundred and thirty, at least one hundred fifty days or at least one hundred and eighty days.

Abstract: The present invention relates to the medical and pharmaceutical use of substituted 1H-imidazo[4,5-c]quinolin-4-amines, in particular Imiquimod® and Gardiquimod®, alone or preferably in combination with Akt inhibitors, in particular with Akti1/2 and AktX, and most preferably with Akti1/2, in the treatment, prevention and/or amelioration of haematological cancers, in particular multiple myeloma disorders or B-cell disorders, and most particular in the therapy of multiple myeloma.

Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors. Also provided are methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

Abstract: The present disclosure is directed to methods of identifying a compound that binds to or interacts with a protein receptor involved in bone formation. Specifically, the disclosure is directed to methods of identifying a compound that regulates a Wnt pathway in a cell by binding to or interacting with cavities in proteins such as LRP5, LRP 6 and/or frizzled receptor and interfering with receptor binding to other proteins in a Wnt pathway. The present disclosure is further directed to methods and compositions that comprise an identified compound for treating or preventing a disease in a mammal in which Wnt pathway suppression plays a role.

Abstract: Compositions of matter including (R)-2,5,6,8-tetramethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine and (R)-2,6,8-trimethyl-8-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)-1,2,3,8,9,10-hexahydrochromeno[5,6-e][1,3]oxazine are disclosed herein. Further disclosed are methods of preparation of such compounds and the use of such compounds as anticancer agents.

Abstract: Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.

Abstract: The loss of the SOST gene product sclerostin leads to sclerosteosis characterized by high bone mass (HBM). In this report, we found that sclerostin could antagonize canonical Wnt signaling in human embryonic kidney A293 cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by over-expression of Wnt coreceptor LRP5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transducing canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at the late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b.

Abstract: Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

Abstract: The present invention concerns methods and compositions involving small molecule inhibitors for the treatment or prophylaxis of flavivirus infection, such as dengue virus and West Nile virus.