Abstract: The present invention is based on the findings that BACE2, a homolog of ?-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A?. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A? production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases by reducing ?-amyloid deposit formation.

Abstract: Peptides comprising the effective portion of human brain natriuretic peptide are provided in pharmaceutical compositions and methods to effect vasodilation and/or natriuresis.

Abstract: The disclosed invention is directed to methods and compounds useful in treating a myelodysplastic syndrome (MDS) using p38 MAP kinase inhibitors either alone or in combination with other chemotherapeutic compounds. A role for p38 kinase inhibition as a treatment modality for combating MDS is discussed herein. Relating to a preferred embodiment, compounds of the invention have been found to inhibit p38 kinase, the ?-isoform in particular, and are useful in treating MDS.

Abstract: The present invention is directed to a method for producing a pyridopyrimidone of the formula wherein X is N or CH and R is an aryl, heteroaryl or alkyl group, said method comprising the step of reacting an acid derivative of the formula: wherein X is N or CH; Y is an appropriate leaving group; Z is a halogen, OR1, NHR1, or SR1; and R1 is a lower alkyl; and the amidine derivative is wherein R is an aryl, heteroaryl or alkyl group.

Abstract: The invention is directed to compounds and methods to inhibit p38 kinase wherein the compounds are a pyrimidine or pyridine coupled to two mandatory substituents.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

Abstract: Immunoassays for the biological precursor of human brain natriuretic peptide are described.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32–39 kDa or 22–26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5–7.0.

Abstract: The invention concerns the prevention and treatment of endothelial injury and the injury of tissues containing injured blood vessels by administration of angiogenic factors, such as vascular endothelial cell growth factor (VEGF).

Abstract: The present invention provides a method to treat multiple myeloma by the administration of one or more p38 MAP kinase inhibitor(s).

Abstract: Disclosed herein are methods for identifying inhibitors of neuronal degeneration, and their use in the treatment of neurodegenerative disorders. In particular methods methods are disclosed for identifying inhibitors of neuronal degeneration or cell death by taking advantage of the involvement of presenilin (PS) and Par-4 in NF-?B activation.

Abstract: The present invention provides a method to treat osteolytic lesions associated with multiple myeloma by the administration of one or more p38 MAP kinase inhibitors.

Abstract: The present invention provides a method to treat multiple myeloma by the co-administration of one or more p38 MAP kinase inhibitors with one or more proteosome inhibitors.

Abstract: Peptides comprising the effective portion of human brain natriuretic peptide are provided in pharmaceutical compositions and methods to effect vasodilation and/or natriuresis.

Abstract: The present invention concerns methods and means for identifying inhibitors of neuronal degeneration, and their use in the treatment of neurodegenerative disorders. In particular the invention concerns methods and means for identifying inhibitors of neuronal degeneration or cell death by taking advantage of the involvement of presenilin (PS) and Par-4 in NF-?B activation.

Abstract: The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically.

Abstract: The invention concerns methods of treating malignant gliomas, by administering inhibitors of TGF-? the TGF-? signaling pathway, including molecules preferably binding to the type I TGF-? receptor (TGF?-R1). Preferably, the inhibitors are non-peptide small molecules, including quinazoline derivatives. The invention also concerns methods for reversing the TGF-?-mediated effect on glioma cells to make them less refractile to signaling and other immune cells, comprising contacting a glioma cell or tissue in vivo or in vitro, with an inhibitor of TGF-?.

Abstract: The invention is directed to methods to inhibit TGF-? and/or p38-? kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar? is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract: Polypeptides capable of regulating signal transduction, which preferably exhibit kinase activity, or antibodies against such polypeptides that inhibit the interaction of these polypeptides with other mediators of signal transduction, may be used in the identification, prevention or treatment of disease, preferably cardiac disease, in mammalian hosts. In addition, these polypeptides can facilitate the identification or isolation of additional mediators of signal transduction associated with disease, preferably cardiac disease, which in turn may also be used in the identification, prevention or treatment of disease, preferably cardiac disease, in mammals.