Abstract: Compositions and methods are provided for treating NF-?B-related conditions. In particular, the invention provides a stimulus-inducible IKK signalsome, and components and variants thereof. An IKK signalsome or component thereof may be used, for example, to identify antibodies and other modulating agents that inhibit or activate signal transduction via the NF-?B cascade. IKK signalsome, components thereof and/or modulating agents may also be used for the treatment of diseases associated with NF-?B activation.

Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective for ER-? over ER-?. Methods are disclosed for modulating ER-? in cell and/or tissues expressing the same, including cells and/or tissue that preferentially ER-?. Methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natureal hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.

Abstract: Benzopyranone Compounds having the following structure: wherein R1, R2, X, Y and n are as defined herein, are disclosed. The Benzopyranone Compounds are useful for treating or preventing a bone-resorbing disease, a neoplastic disease, arthritis, a disease exacerbated by the presence of estrogen or a disease improved by the presence of estrogen, comprising administering an effective amount of a Benzopyranone Compound to a patient in need of the treating or preventing; activating the function of estrogen receptor (“ER”) in a bone cell; inhibiting the function of ER in a cancer cell; inhibiting the expression of interleukin-6 (“IL-6”) in a cell; and inhibiting the growth of a neoplastic cell, comprising contacting the cell with an effective amount of a Benzopyranone Compound.

Abstract: Compounds having activity as selective inhibitors of JNK are disclosed. The compounds of this invention are indazole derivatives having the following structure: wherein R1, R2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: This invention is generally directed to Indazole Derivatives having the following structure: or pharmaceutically acceptable salt thereof, wherein R1, R2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of diseases and disorders that are responsive to JNK inhibition, such as an inflammatory disease or disorder. Thus, methods of treating such diseases and disorders are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: Compounds having activity as selective inhibitors of JNK are disclosed. The compounds of this invention are indazole derivatives having the following structure: wherein R1, R2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: Compositions and methods are provided for the treatment of diseases associated with mitogen activated protein kinase cascades. In particular, the mitogen-activated protein kinase p38-2, and polypeptide variants thereof that stimulate phosphorylation and activation of substrates such as ATF2, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the p38-2 kinase cascade. Such polypeptides and agents may also be used for the treatment of diseases associated with mitogen-activated protein kinase cascades.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: This invention relates to methods for using benzopyranones, or their pharmaceutically acceptable salts, for treating or preventing a primary brain cancer or a brain metastasis. The benzopyranones have the formula: wherein R1, R2, R3, n and p are as defined herein.

Abstract: Compounds having activity as inhibitors of the JNK pathway are disclosed. The compounds of this invention are anilinopyrimidine derivatives having the following structure: wherein R1 through R6 are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to inhibition of the JNK pathway. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: Compounds having activity as inhibitors of IKK are disclosed, particularly IKK-2. The compounds of this invention are anilinopyrimidine derivatives having the following structure: wherein R1 and R6 are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to IKK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: Compounds having activity as selective inhibitors of JNK are disclosed The compounds of this invention are pyrazoloanthrone and derivatives thereof having the following structure: wherein R1 and R2 are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: This invention relates to Benzopyranone Compounds, compositions comprising a Benzopyranone Compound and methods for treating or preventing cancer or inhibiting the growth of a cancer cell or neoplastic cell comprising administering an effective amount of a Benzopyranone Compound. The Benzopyranone Compounds have the formula: or a pharmaceutically acceptable salt thereof, wherein R1 is halogen, trifluoromethyl or C1-6 alkyl.

Abstract: The present invention generally relates to compounds and compositions useful for the modulation of ligase activity. The invention further relates to Compounds of the Invention, compositions thereof, and methods for treating or preventing cancer, a neoplastic disorder, acute or chronic renal failure, an inflammatory disorder, an immune disorder, a cardiovascular disease, an effect of aging or an infectious disease comprising administering an effective amount of a Compound of the Invention. The invention further relates to the use of a Compound of the Invention as a preservative of a cell, blood, tissue or an organ or as an agent to modulate stem cells.

Abstract: Isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof having the general formula: and pharmaceutically acceptable salts thereof, wherein R0 is —CH2—, —SO—, —O—, —SO2—, or —S—; compositions comprising the isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof; and methods for treating or preventing a disorder alleviated by inhibiting Jun N-terminal kinase (JNK) by administering the isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof are described herein.

Abstract: Methods are provided for the isolation of newly synthesized mRNA. Such methods involve the incorporation of biotinylated rNTP analogues into cellular mRNA, and separating biotinylated mRNA from unlabeled RNA. The methods provided herein may be used, for example, for gene discovery, drug screens and studies of the regulation of gene expression.

Abstract: Conditionally-immortalized human mesencephalon cell lines are provided. Such cell lines, which may be clonal, may be used to generate neurons, including dopaminergic neurons. The cell lines and/or differentiated cells may be used for the development of therapeutic agents to prevent and treat a variety of neurological diseases such as Parkinson's disease. The cell lines and/or differentiated cells may also be used in assays and for the general study of mesencephalon cell development and differentiation.

Abstract: Compounds having activity as selective inhibitors of JNK are disclosed. The compounds of this invention are indazole derivatives having the following structure: wherein R1, R2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Abstract: Conditionally-immortalized PNS progenitor cell lines are provided. Such cell lines, which may be clonal, may be used to generate neurons. The cell lines and/or differentiated cells may be used for the development of therapeutic agents to prevent and treat a variety of PNS-related diseases. The cell lines and/or differentiated cells may also be used in assays and for the general study of PNS cell development, death and abnormalities.

Abstract: Compositions and methods are provided for potentiating the activity of the mitogen-activated protein kinase p38. In particular the mitogen-activated protein kinase kinase MEK6, and variants thereof that stimulate phosphorylation of p38 are provided. Such compounds may be used, for example, for therapy of diseases associated with the p38 cascade and to identify antibodies and other agents that inhibit or activate signal transduction via p38.