Abstract: A method of synthesizing a chiral compound having a quaternary carbon atom bearing diastereotopic groups from (a) a nitroolefin and (b) an ?-substituted ?-dicarbonyl or an equivalent compound having an acidic C—H moiety compound is disclosed. A subsequent intramolecular reaction between one of the substituents comprising the stereogenic carbon atom and one of the diastereotopic groups comprising the quaternary carbon atom creates a new compound having two contiguous stereogenic centers, one of which is quaternary, with control over the relative stereochemistry.

Abstract: The present invention relates in part to compounds of formulas I and III: and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.

Abstract: The present invention relates to improved methods for inhibiting aberrant cell proliferation involving the scheduling of administration of Chk1 activators (e.g., chemotherapeutic agents) and Chk1 inhibitors. At least one Chk1 activator is administered at a dose and for a time sufficient to induce substantial synchronization of cell cycle arrest in proliferating cells. Upon achieving substantial phase synchronization, at least one Chk1 inhibitor is administered to abrogate the cell cycle arrest and induce therapeutic cell death. The invention is useful with any Chk1 activator and any Chk1 inhibitor, and finds application in treating or preventing cancerous and non-cancerous aberrant cell proliferation.

Abstract: Methods to treat secondary injury resulting from spinal cord injury using polypeptide compositions that specifically bind to CD11d are disclosed.

Abstract: Compounds that inhibit DNA-dependent protein kinase, compositions comprising the compounds, methods to inhibit the DNA-PK biological activity, methods to sensitize cells the agents that cause DNA lesions, and methods to potentiate cancer treatment are disclosed.

Abstract: Novel pyrrolidine compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: Methods to inhibit inflammation and macrophage infiltration following spinal cord injury are disclosed along with methods to modulate TNF? release from cells expressing ?d are disclosed.

Abstract: The present invention provides novel purified and isolated nucleotide sequences encoding the cGMP-binding, cGMP-specific phosphodiesterase designated cGB-PDE. Also provided by the invention are methods and materials for the recombinant production of cGB-PDE polypeptide products and methods for identifying compounds which modulate the enzymatic activity of cGB-PDE polypeptides.

Abstract: Pyrazole compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

Abstract: The present invention relates to methods for making multimeric proteins comprising fusion of two or more cells expressing a single subunit of the multimeric protein to generate a single hybrid cell expressing the fully assembled multimeric protein.

Abstract: The invention relates generally to methods for treating and/or preventing aberrant proliferation of hematopoietic cells. More particularly, the invention relates to methods for treating and/or preventing aberrant proliferation of hematopoietic cells comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3K?) activity in hematopoietic cells. The methods may be used to treat any indication involving aberrant proliferation of hematopoietic cells.

Abstract: Novel pyrrolidine compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: The present invention provides purified and isolated polynucleotide sequences encoding a novel macrophage-derived C—C chemokine designated “Macrophage Derived Chemokine” (MDC), and polypeptide fragments and analogs thereof. Also provided are materials and methods for the recombinant or synthetic production of the chemokine, fragments, and analogs; and purified and isolated chemokine protein, and polypeptide fragments and analogs thereof. Also provided are antibodies reactive with the chemokine and methods of making and using all of the foregoing. Also provided are assays for identifying modulators of MDC chemokine activity.

Abstract: The present invention provides purified and isolated polynucleotide sequences encoding a novel macrophage-derived C-C chemokine designated “Macrophage Derived Chemokine” (MDC), and polypeptide fragments and analogs thereof. Also provided are materials and methods for the recombinant or synthetic production of the chemokine, fragments, and analogs; and purified and isolated chemokine protein, and polypeptide fragments and analogs thereof. Also provided are antibodies reactive with the chemokine and methods of making and using all of the foregoing. Also provided are assays for identifying modulators of MDC chemokine activity.

Abstract: Novel pyrrolidine compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: The invention provides a novel human poly(ADP-ribose) polymerase (hPARP2) polypeptides, polynucleotides encoding the polypeptides, expression constructs comprising the polynucleotides, and host cells transformed with the expression constructs. Also provided are methods for producing the hPARP2 polypeptides, antibodies that are immunoreactive with the hPARP2 polypeptides. In addition, there are provided methods for identifying specific binding partners of hPARP2, and more particularly methods for identifying binding partners that modulate biological activity of hPARP2. Methods of modulating biological activity of hPARP2 in vitro and in vivo are also provided.

Abstract: The present invention provides polynucleotides that encode the chemokine receptors 88-2B or 88C and materials and methods for the recombinant production of these two chemokine receptors. Also provided are assays utilizing the polynucleotides which facilitate the identification of ligands and modulators of the chemokine receptors. Receptor fragments, ligands, modulators, and antibodies are useful in the detection and treatment of disease states associated with the chemokine receptors such as atherosclerosis, rheumatoid arthritis, tumor growth suppression, asthma, viral infection, AIDS, and other inflammatory conditions.

Abstract: Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K?) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3K? plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K5, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K? activity, including compounds that selectively inhibit PI3K? activity. Methods of using PI3K? inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K? inhibitory compounds to inhibit PI3K?-mediated processes in vitro and in vivo.

Abstract: Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.