Abstract: Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract: The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.

Abstract: Oligopeptides which can be used to treat cancer are disclosed. Further disclosed are methods of treating cancer, including breast cancer, skin cancer, prostate cancer and multiple myeloma (MM). These methods include administration of a polypeptide encoded by the Mesd gene, or an oligopeptide comprising a contiguous subsequence of a Mesd polypeptide.

Abstract: Fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labelled with 18F, can be used as radiotracers for imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labelled with 123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.

Abstract: A series of N-substituted 9-azabicyclo[3.3.1]nonan-3?-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (?1 and ?2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for ?2 versus ?1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the ?2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

Abstract: Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kd of less than about 10?7 M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

Abstract: Methods are disclosed for decreasing stem cell proliferation, including cancer stem cell proliferation. These methods comprise administering to stem cells inhibitors of AMP activated protein kinase (AMPK). Methods for promoting stem cell growth by increasing stem cell proliferation, self-renewal and/or differentiation are also disclosed. These methods comprise administering AMPK activators to stem cells. Methods of achieving selective differentiation of stem cells are also disclosed. These methods comprise administering small molecules to stem cells that modulate AMPK activity. Applications of these methods are also disclosed, such as methods of increasing numbers of neuronal progenitor cells. These methods can be used therapeutically, such as for repair of spinal cord injuries, or for stimulating neurogenesis in the hippocampus, and other cell-based therapies. The methods can also be used for screening of compounds that can be activators or inhibitors of AMPK activity.

Abstract: Fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labelled with 18F, can be used as radiotracers for imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labelled with 123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.

Abstract: Methods for detection of cancer cells and for determining the proliferative status of cells in a tissue sample in vitro are disclosed. These methods comprise contacting a tissue sample with a radiolabeled compound or salt thereof of Formula wherein at least one of X, Y, and Z comprises a radioisotope, n is an integer from 2 to about 10; and each of A and A1 is a C1-C4 alkoxyl, a C1-C4 fluoroalkyl or a C1-C4 fluoroalkoxyl. The methods further comprise detecting the distribution of the radioisotope in the tissue sample, whereby a cell having a high density of the radioisotope compared to quiescent cells is diagnostic for a cancer cell.

Abstract: A norovirus-permissive cell culture infected with a norovirus, and methods of culturing a norovirus, are disclosed. Norovirus-permissive cells include dendritic cell-lineage cells, and macrophage-lineage cells, such as dendritic cells, and macrophages having a deficiency in a cellular anti-viral pathway such as a STAT-1-dependent pathway, an interferon receptor-dependent pathway, or a PKR-dependent pathway. Also disclosed are methods of screening anti-viral compounds against norovirus-permissive cells infected with norovirus, and norovirus adapted to grow in fibroblasts as well as macrophages that are not deficient in a cellular anti-viral pathway. Methods of making a norovirus vaccine are also disclosed. A replicative form of norovirus as well as its use in the development of an anti-viral agent and a polypeptide expression system are also described. Further disclosed are methods of detecting norovirus in a sample.

Abstract: Methods of treating or preventing axonal degradation in neuropathic diseases in mammals are disclosed. The methods can comprise administering to the mammal an effective amount of an agent that acts by increasing sirtuin activity in diseased and/or injured neurons. The methods can also comprise administering to the mammal an effective amount of an agent that acts by increasing NAD activity in diseased and/or injured neurons. Also disclosed are methods of screening agents for treating a neuropathies and recombinant vectors for treating or preventing neuropathies.

Abstract: The invention disclosed herein relates to a newly discovered murine norovirus, and compositions and methods related thereto.