Abstract: This invention relates to methods for identifying agents useful for treatment of diseases and pathological conditions affected by Retinoid X Receptor apoptosis. The invention also relates to methods for treating diseases and pathological conditions affected by RXR apoptosis. The invention includes compositions that are useful in the study and treatment of diseases and pathological conditions affected by RXR apoptosis.

Abstract: Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently H, C(O)X, C(O)NHX, NH(CO)X, SO2NHX, or NHSO2X, wherein X is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycle, or substituted heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

Abstract: Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently H, C(O)X, C(O)NHX, NH(CO)X, SO2NHX, or NHSO2X, wherein X is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycle, or substituted heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: A hybrid annotation and publication system can access content in a scalable manner from databases, allowing for its editing and publication via wiki-style programs, while at the same time allowing for peer-review of such content via peer-review programs. This system balances the wiki-style programs, the peer-review programs, and any database store accesses in a manner appropriate to the need at hand according to various heuristics. For instance, the system can be accessed via a web browser, and data provided from various databases can be edited. Such data can be stored in the system in a hierarchical manner. Once the content is annotated, it can be reviewed (at various levels, ranging from expert to novice). Upon review, such content can be published using the wiki programs, so that the content is ready for public and/or private consumption.

Abstract: Neurite outgrowth-promoting prostaglandins (NEPPs) and other electrophilic compounds bind to Keap1, a negative regulator of the transcription factor Nrf2, and prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of neuronal cells. Therefore, neuroprotective compositions and related methods are provided that employ such neuroprotective compounds, and prodrugs of such compounds, to cause dissociation of Nrf2 from a Keap1/Nrf2 complex.

Abstract: Methods of identifying death receptor sensitizing compounds and methods of using death receptor sensitizing compounds are provided.

Abstract: The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.

Abstract: In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPS) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

Abstract: The present invention provides a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature. The invention also provides a method of directing a moiety to tumor lymphatic vasculature in a subject by administering to the subject a conjugate containing a moiety linked to a homing molecule that selectively homes to tumor lymphatic vasculature.

Abstract: The present invention relates to a peptide, which specifically homes to the intracranial, early stage astrocytoma model that grows as islets and harbors co-opted tumor vessels in the brain. The peptide finds its use in targeted delivery of therapeutic substances to invasive brain cancer or metastatic brain lesions as such and in combination with conventional therapies, such as surgery and radiation, and anti-angiogenic therapies, and as a tool in diagnosis of, e.g., invasive brain cancer or metastatic brain lesions.

Abstract: The present invention provides compounds having the general structure I, or a pharmaceutically acceptable salt thereof: wherein X is a six-member ring selected from phenyl, pyridine, or pyrimidine; Y is H, an alkenyl, a substituted alkenyl, or alkynyl, and R is H or alkyl. Pharmaceutical compositions for treating various disorders such as cancers, the compositions including compound I are also provided.

Abstract: The invention provides compounds that can efficiently and specifically inhibit bacterial toxins, such as inhibit the lethal factor (LF) protease activity of anthrax toxin and/or botulinum neurotoxin type A. The invention also provides methods for inhibiting proteases, such as lethal factor protease, as well as methods for treating bacterial infections, such as anthrax and botulinum.

Abstract: Disclosed herein are compositions of nanoparticles. In some embodiments, the nanoparticles are Janus particles, where each particle includes a first component and second component that are exposed to the surface of the particle. Also, disclosed are methods and systems for making a composition of nanoparticles. Finally, a method of treating a mammal by administering a composition of nanoparticles is disclosed.

Abstract: The present invention provides compound having the general structure A or pharmaceutically acceptable salts thereof: Het-L-P??(A) wherein Het is an aromatic moiety comprising a heterocyclic structure mimicking ATP, P is a docking site derived peptide or a docking site peptide mimetic, and L is a linking moiety, wherein L links the ATP mimetic to the docking site peptide moiety. The compounds having the general structure A can serve as inhibitors of kinases, such as the kinases JNK, Erk and p38.

Abstract: Compositions and methods are provided for screening for compounds that modulate insulin promoter activity. Vectors that express green fluorescent protein under the control of the human insulin promoter are introduced into mouse and human cells in which the insulin promoter is expressed in a glucose-responsive manner. Such cells are then used to screen for compounds that modulate insulin promoter activity.

Abstract: There are provided methods of inhibiting growth and metastasis of melanoma, methods of sensitizing melanoma cells to apoptosis, and methods of treating a subject having melanoma using acetyl isogambogic acid, celastrol, or a derivative thereof. There are further provided derivatives of celastrol and compositions comprising acetyl isogambogic acid, celastrol, or a derivative thereof.

Abstract: The invention provides Bcl-G polypeptides and encoding nucleic acids. Bcl-G polypeptides include Bcl-GL and Bcl-GS. The invention also provides mouse Bcl-G. The invention also provides vectors containing Bcl-G nucleic acids, host cells containing such vectors, Bcl-G anti-sense nucleic acids and related compositions. The invention additionally provides Bcl-G oligonucleotides that can be used to hybridize to or amplify a Bcl-G nucleic acid. Anti-Bcl-G specific antibodies are also provided. Further provided are kits containing Bcl-G nucleic acids or Bcl-G specific antibodies. Such kits and reagents can be used to diagnose cancer, monitor response to therapy, or predict the prognosis of a cancer patient. The invention additionally provides methods of modulating apoptosis using Bcl-G polypeptides, encoding nucleic acids, or compounds that modulate the activity or expression of Bcl-G polypeptides. The methods for modulating apoptosis can be used to treat diseases such as cancer.

Abstract: The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate C. elegans (BAG-1, BAG-2) and the fission yeast S. pombe (BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Abstract: Compositions useful for inhibiting the growth of bacteria, including bacteria that can cause gastric ulcers, are provided. In addition, transgenic organism that can produce such compositions are provided. Methods of using the compositions to treat or prevent gastric ulcers in a subject, including a human subject, also are provided.