Abstract: This invention relates to monoclonal antibodies that recognize modified &bgr;-tubulin isotypes, methods of using such antibodies to detect modified &bgr;-tubulin isotypes, methods of using such antibodies to monitor &bgr;-tubulin modifying agents administered to a patient, methods of using such antibodies to isolate modified &bgr;-tubulin, and methods of detecting the anti-modified &bgr;-tubulin antibodies.

Abstract: Compounds, compositions and methods that are useful in the treatment of immunoregulatory conditions and disorders are provided herein. In particular, the invention provides compounds which modulate the function of a Signal Transducer and Activator of Transcription (STAT) protein. The compounds are represented by the general formula: wherein Y, Ar, X, A2, A1, R1 and R2 are defined herein. The compounds are useful to treat, for example, allergic and inflammatory conditions and disorders.

Abstract: The invention relates to serine protease inhibitor compounds of formula (I) where R1 is hydrogen, halo, cyano, nitro or hydroxyl, amino, alkoxy, alkyl, aminoalkyl, hydroxyalkyl, thiol, alkylthio, aminosulphonyl, alkoxyalkyl, alkoxycarbonyl, acyloxymethoxycarbonyl or alkylamino optionally substituted by hydroxy, alkylamino, alkoxy, oxo, aryl, cycloalkyl, amino, halo, cyano, nitro, thiol, alkylthio, alkylsulphonyl, alkylsulphenyl, alkylsulphonamido, alkylaminosulphonyl, haloalkoxy and haloalkyl; R2 is hydrogen, halo, methyl, amino, hydroxy, or oxo; and R is X—X—Y(R7)—L—Lp(D)n; wherein each X independently is C, N, O or S atom or a CO, CR1, C(R1)2 or NR1 group, at least one X being C, CO, CR1 or a C(R1)2 group; Y (the &agr;-atom) is a nitrogen atom or a CR1 group or Y and L taken together form a cyclic group; R7 is a lipophilic group selected from alkyl, alkenyl, mono- or bi-cycloalkyl, aryl, heteroaryl, mono- or bicycloalkylalkyl, mono- or bicycloalkylalkenyl, aralkyl,

Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: The invention provides methods and compositions relating to Suppressor of Death Domain (SODD) proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SODD encoding nucleic acids or purified from human cells. The invention provides isolated SODD hybridization probes and primers capable of specifically hybridizing with the disclosed SODD genes, SODD-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: Salts of pyrimidine derivatives are provided having the formula: wherein R represents hydrogen, methyl or ethyl; Z represents a substituted or unsubstituted 1-piperidinyl, a substituted or unsubstituted 4-morpholinyl, or a substituted or unsubstituted 1-pyrrolidinyl; and Ar represents a substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl. These salts are particularly useful as antiviral agents (e.g., to treat CMV infections).

Abstract: The invention provides compounds, compositions and methods relating to novel electrophilic aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: Certain six-membered aromatic and heteroaromatic-dioxobutyric acid derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: The invention provides methods and compositions for diagnosing and treating tumors. In particular embodiments, the invention provides methods for characterizing tumors for SODD gene copy number and/or expression and for using this diagnosis in guiding treatment options. Accordingly, the invention provides methods for biasing therapeutic options by (a) contacting a biopsy of a tumor with an agent which specifically binds a SODD gene or SODD gene product thereof; (b) measuring specific binding of the agent to the SODD gene or gene product to determine an amount of the SODD gene or gene product present in the biopsy; and (c) biasing therapeutic options for treating the tumor based on the amount of the SODD gene or gene product present in the biopsy.

Abstract: T2K kinase activity is detected by forming a mixture of a T2K kinase and a substrate; incubating the mixture under conditions whereby the kinase phosphorylates the substrate at a first rate; and detecting the first rate as an indication of the kinase activity. The substrate comprises SX1X2X3SX4 (SEQ ID NO:1) wherein X1 and X4 are aliphatic residues and both of the S residues are targets of the kinase, and especially, IKK&agr; or IKK&bgr;. In another embodiment, the mixture substrate comprises a particular IL-1 or TNF signaling cascade component. The mixture may be used to screen for agents which modulate the activity of the kinase, e.g. as an immuno-chemiluminescent assay.

Abstract: Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic platinum coordination complex such as cisplatin.

Abstract: The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

Abstract: This invention relates to monoclonal antibodies that recognize modified &bgr;-tubulin isotypes, methods of using such antibodies to detect modified &bgr;-tubulin isotypes, methods of using such antibodies to monitor &bgr;-tubulin modifying agents administered to a patient, methods of using such antibodies to isolate modified &bgr;-tubulin, and methods of detecting the anti-modified &bgr;-tubulin antibodies.

Abstract: Nitrogen-containing heteroaryl dioxo-butyric acid derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: Modulators of PPAR&ggr; activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

Abstract: The invention provides methods and compositions relating to CPF proteins which regulate transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed CPF encoding nucleic acids or purified from human cells. The invention provides isolated CPF hybridization probes and primers capable of specifically hybridizing with the disclosed CPF genes, CPF-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: The invention concerns novel inhibitors of tumor necrosis factor receptor associated factor-(TRAF) mediated signal transduction. The invention encompasses the novel inhibitor proteins (I-TRAFs), nucleic acid encoding them, methods for their recombinant production, and their use in screening assays and as pharmaceuticals.

Abstract: The invention provides compounds, compositions and methods relating to novel electrophilic aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.