Abstract: The invention provides compounds and methods for modulating the Hedgehog signaling pathway. The compounds modulate the translocation and/or accumulation of smoothened to the primary cilia.

Abstract: The present invention relates to a compound of formulas I, Ia, Ib and II, wherein R1 to R11 are herein defined.

Abstract: Compounds, compositions and methods for the treatment of retinal degenerative diseases, such as retinitis pigmentosa, Leber's congenital Amaurosis, Syndromic retinal degenerations, age-related macular degeneration and Usher Syndrome, and hearing loss associated with Usher Syndrome are described herein.

Abstract: Methods of inducing mucosal immunity in individuals against proteins and peptides are disclosed. The methods comprise the step of administering topically or by lavage into mucosal tissue selected from the group consisting of rectal, vaginal, urethral, sublingual and buccal, a nucleic acid molecule that comprises a nucleotide sequence that encodes a protein or peptide that comprises an epitope against which mucosal immunity is desired. The methods may be used to immunize and individual against a pathogen infection, hyperproliferative diseases or autoimmune diseases using nucleic acid molecules which encode proteins and peptides that share an epitope with a pathogen antigen or protein associated with cells involved in hyperproliferative diseases or autoimmune diseases, respectively.

Abstract: The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Abstract: Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

Abstract: Novel difluorophenyldiacylhydrazide derivatives of the formula I, in which R1, R2, R3, R4, R5, R6 and R7 have the meanings indicated in claim 1, are kinase inhibitors and can be used for the treatment of diseases and complaints such as diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in any type of fibroses, inflammatory processes, tumours and tumour diseases.

Abstract: Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, and Pichinde), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

Abstract: The present invention is directed to a method of enhancing TGF-? signaling in a subject comprising administering to said subject a clathrin-dependent endocytosis inhibitor in an amount sufficient to enhance TGF-? signaling. In another aspect, the invention is directed to a method of treating a condition associated with decreased TGF-? signaling in a patient in need thereof comprising administering to said patient a clathrin-dependent endocytosis inhibitor in a therapeutically effective amount.

Abstract: A method of treating or preventing an abnormality of glucose metabolism in a subject, the method comprising administering an antagonist of Inhibitor of Differentiation 1 (Id1) to the subject.

Abstract: The present invention provides materials and methods for modulating an immune response. The materials and methods may be used to treat diseases associated with an aberrant immune response. In some embodiments, materials and methods of the invention may be used to treat autoimmune diseases, for example, rheumatoid arthritis.

Abstract: The invention relates to novel guanidine derivatives in the cinnamic series of general formula (I): The invention also relates to the process for preparing said guanidine derivatives and also to synthetic intermediates. Finally, the invention relates to the use of the guanidine derivatives for the preparation of compositions with anti-glycation properties, especially in cosmetology.

Abstract: Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, and Pichinde), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

Abstract: This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Abstract: The present document describes a cancer mutation-selective chemosensitizer that comprise compounds for restoring association between mutated keap1 protein and Nrf2 protein, and inhibition of Nrf2 functions. The present document also describes composition of matter containing the compounds, as well as methods of medical treatment for treating diseases such as cancer with the compounds.

Abstract: Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.

Abstract: The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.

Abstract: The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N?-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N?-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

Abstract: The present invention relates to a compound of the general formula (III):

Abstract: Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

Abstract: This disclosure concerns the discovery of the use of fenoterol and (R,R)- and (R,S)-fenoterol analogues for the treatment of a tumor expressing a ?2-adrenergic receptor, such as a primary brain tumor, including a glioblastoma or astrocytoma expressing a ?2-adrenergic receptor. In one example, the method includes administering to a subject a therapeutically effective amount of fenoterol, a specific fenoterol analogue or a combination thereof to reduce one or more symptoms associated with the tumor, thereby treating the tumor in the subject.

Abstract: The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.

Abstract: The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.

Abstract: This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERR? activity to the subject. Such agents can include one or more ERR? agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).

Abstract: A method is disclosed wherein semapimod, and/or the mesylate salt thereof, is administered for the treatment of necrotizing enterocolitis.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Q is O or S; Z1 and Z2 are each independently CR9 or N; and R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

Abstract: Methods of introducing genetic material into cells of an individual and compositions and kits for practicing the same are disclosed. The methods comprise the steps of contacting cells of an individual with a polynucleotide function enhancer and administering to the cells, a nucleic acid molecule that is free of retroviral particles. The nucleic acid molecule comprises a nucleotide sequence that encodes a protein that comprises at least one epitope that is identical or substantially similar to an epitope of a pathogen antigen or an antigen associated with a hyperproliferative or autoimmune disease, a protein otherwise missing from the individual due to a missing, non-functional or partially functioning gene, or a protein that produces a therapeutic effect on an individual. Methods of prophylactically and therapeutically immunizing an individual against HIV am disclosed. Pharmaceutical compositions and kits for practicing methods of the present invention are disclosed.

Abstract: The present invention relates to the use of inhibitors of scavenger receptor class proteins, in particular ScarB1 for the production of a medicament for treatment of and/or prophylaxis against infections, involving liver cells and/or hematopoietic cells, in particular malaria.

Abstract: The subject invention relates in part to the oral administration of ecdysteroids for controlling subterranean termites. Preferred ecdysteroids for use according to the subject invention are ecdysone, certain ecdysone analogs, and 20-hydroxyecdysone, for example. In some preferred embodiments, one or more of these compounds is used in a termite bait in combination with one or more chitin synthesis inhibitors. Thus, the subject invention also relates in part to controlling termites by the use of a chitin synthesis inhibitor (CSI), such as hexaflumuron and/or noviflumuron, together with an ecdysteroid (and analogs thereof) or molt-accelerating compound (MAC), such as halofenozide. The subject invention also relates to mixtures comprising these two active ingredients. The MAC/ecdysteroid analog induces a preliminary molting event in termite workers (they could not complete the molting), which then allows the CSI to further disrupt the molt and cause mortality.

Abstract: Compounds are described that are useful for treating an apoptosis-associated disease, which are specifically cytotoxic to tumor cells that are overexpressing Bcl-xL, and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-xL. Also described is a method for treating an apoptosis-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an active compound that is specifically cytotoxic to tumor cells that are overexpressing Bcl-xL, and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-xL. Several scaffolds of active compounds are described.

Abstract: In one aspect, the invention relates to compounds and methods useful for activating heme sensor systems; for decreasing virulence of bacteria, for example, Staphylococcus aureus; pharmaceutical compositions comprising the compounds; and methods of treating microbial-related disorders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.

Abstract: The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. To this end, the inventors have identified small molecule compounds that inhibit bacterial target enzymes by interacting with a novel inhibitory binding site on the enzyme while having no effect on functionally equivalent human enzymes.

Abstract: Provided are various compounds of Formula (I): Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract: Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

Abstract: 3D protein modeling and virtual screening of commercially-available compounds were performed to identify new inhibitors of the herpesvirus DNA polymerase, a key enzyme in the viral replication cycle. Two compounds (Nos 2 and 9) were particularly active against HSV-1 and HSV-2 strains and one compound (No 3) inhibited specifically cytomegalovirus (CMV) strains (overall hit rate of 25%). Some of the tested compounds inhibited wild-type viruses and strains resistant to current antiviral agents. New chemical entity derivatives of compound 2 with binding potential to the DNA polymerase retained an excellent activity against HSV-1, HSV-2 and VZV like the parental compound, as well against strains resistant to current antiviral agents. These non-nucleosidic herpesvirus DNA polymerase inhibitors with in vitro activity against drug-resistant clinical isolates warrant further pre-clinical studies.

Abstract: Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, and Pichinde), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

Abstract: There is provided a method for promoting dynamin ring formation and/or maintenance of dynamin rings in a cell, comprising treating the cell with an effective amount of a dynamin ring stabilizer, or a prodrug or pharmaceutically acceptable salt of the dynamin ring stabilizer. The maintenance or accumulation of dynamin ring formation has particular application in the prophylaxis or treatment of a kidney disease or condition characterized by proteinuria. A dynamin ring stabilizer can be any agent that interacts with dynamin to promote dynamin ring assembly and/or inhibit dynamin ring disassembly. There are also provided methods for prophylaxis or treatment of podocyte dysfunction and/or maintaining or inducing actin cytoskeleton formation in a cell utilizing dynamin ring stabilizers, and for screening a test agent for use as a dynamin ring stabilizer.

Abstract: An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and represents a single bond or a double bond, R5 represents optionally substituted aryl or the like, Z represents —N?CHR6R7 or the like, R6 and R7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R101 and R102 together form ?O, and R103 and R104 represent H, or R101 and R104 together from a bond, and R102 and R103 together form a bond.

Abstract: There is a harmful organism that cannot be controlled or is difficult to be controlled with the use of a single agent of a compound represented by the general formula (1) according to the invention, an insecticide, a miticide or a fungicide. Accordingly, an object of the invention is to provide a composition for preventing harmful organisms for efficiently controlling such a harmful organism.

Abstract: Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

Abstract: Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, and Pichinde), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

Abstract: Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Abstract: The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

Abstract: The present invention relates to a composition containing bifeprunox or its N-oxide, or at least one pharmacologically acceptable salt thereof: and L-DOPA or at least one pharmacologically acceptable salt thereof, for simultaneous, separate or sequential use in the treatment of disorders requiring recovery of dopaminergic function, including Parkinson's disease and restless leg syndrome.

Abstract: A treatment to differentially regulate the expression of genes related to irritable bowel syndrome is provided.

Abstract: Disclosed are dihydrazide compounds having formula (I) or (II), wherein R1-R4 are alkylene, substituted alkylene, aryl or polyether radical. The preparation and uses for producing medical hydrogel and medicine controlled releasing carrier of said dihydrazide compounds are provided.