Abstract: Compounds that inhibit p38a MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

Abstract: Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a generic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compound 6jc48-1 ((E)-2,4-bis(4-bromophenyl)-6-(4-(dimethyl-amino)styryl)pyrylium boron tetrafluoride salt) binds to Lipid II with high affinity, has markedly reduced cytotoxicity than BAS00127538, and retains activity against drug-resistant strains of Enterococci. It is stable in plasma, has dramatically improved pharmacokinetic and pharmacodynamics properties, and possesses in vivo efficacy in a mouse model of sepsis.

Abstract: Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a genetic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compounds bind to Lipid II with high affinity, have markedly reduced cytotoxicity compared to BAS00127538, and retain activity against drug-resistant strains of Enterococci. They are stable in plasma, have dramatically improved pharmacokinetic and pharmacodynamics properties, and possess in vivo efficacy in a mouse model of sepsis.

Abstract: Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a generic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compounds bind to Lipid II with high affinity, have markedly reduced cytotoxicity compared to BAS00127538, and retain activity against drug-resistant strains of Enterococci. They are stable in plasma, have dramatically improved pharmacokinetic and pharmacodynamics properties, and possess in vivo efficacy in a mouse model of sepsis.

Abstract: Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a generic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compound 6jc48-1 ((E)-2,4-bis(4-bromophenyl)-6-(4-(dimethyl-amino)styryl)pyrylium boron tetrafluoride salt) binds to Lipid II with high affinity, has markedly reduced cytotoxicity than BAS00127538, and retains activity against drug-resistant strains of Enterococci. It is stable in plasma, has dramatically improved pharmacokinetic and pharmacodynamics properties, and possesses in vivo efficacy in a mouse model of sepsis.

Abstract: The present invention is drawn to therapeutics and methods of inhibiting signaling by TLR2. The invention provides a method of treating an inflammatory disease or condition in a subject comprising administering to the subject a therapeutically effective amount of a compound of the invention or salt, solvate, hydrate, prodrug, metabolite, or combination thereof.

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: 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 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: 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: An object of the present invention is to provide compounds having read-through activity for use in treatment methods of genetic diseases caused by nonsense mutation, to provide pharmaceutical compositions comprising the compound, and to provide a treatment method of genetic diseases caused by nonsense mutation comprising administering the compound. The present invention can provide a method of producing wild type normal protein in a living body of a mammal from a gene with a premature termination codon being generated by a mutation, wherein the method comprises administering a compound expressed by the following formula (VI): (wherein R1, R2, R3, R4, R5 and X1 in the formula are as defined in description) or the like to the mammal.

Abstract: Compounds are described which modulate the tzrosine kinase activity of p56lck and signal transduction pathways in which this enzyme is involved. The invention also relates to compounds which have immunomodulatory activity, e.g., which have immunosuppressant or immunostimulatory activity, and/or which have an antineoplastic effect. The invention further relates to compositions comprising these compounds, and methods of using them. Compounds are described which modulate the tyrosine kinase activity of p56.

Abstract: Small molecular-weight non-peptidic compounds block Lck SH2 domain-dependent interactions. The inhibitors omit phosphotyrosine (pY) or related moieties.

Abstract: Small molecular-weight non-peptidic compounds block Lck SH2 domain-dependent interactions. The inhibitors omit phosphotyrosine (pY) or related moieties.

Abstract: Provided herein are compounds and methods of using compounds that selectively inhibit binding to one or more docking domain regions of an extracellular signal-regulated kinase (ERK) to inhibit in a cell having an extracellular signal-regulated kinase activity. Such methods may be used to inhibit cell proliferation of a neoplastic cell, to treat a cancer and further may be used in conjunction with administration of an anticancer drug at a reduced dosage to treat a cancer with a concomitant reduction in toxicity to an individual receiving the treatment. Also provided is a method to design and screen for compounds to inhibit binding within the extracellular signal-regulated kinase docking domain region, using at least in part computer-aided drug design modeling.

Abstract: Compounds that bind S100 and inhibit the S100-p53 protein-protein interaction and activate the tumor suppressor activity of p53, and thus which have an antineoplastic effect are disclosed, as well as methods for identifying these compounds, compositions comprising the same, and methods of using the same to treat cancer.