Abstract: This invention describes a method of removing N-terminal alanine residues from polypeptides, preferably recombinant proteins, using an aminopeptidase derived from the marine bacterium Aeromonas proteolytica. Accordingly, Aeromonas aminopeptidase (AAP; E.C. 3.4.11.10) can be used to remove N-terminal alanyl residues from derivatives of human somatotropin (hST, human growth hormone, or hGH), porcine somatotropin (pST), and bovine somatotropin (bST), for example, to yield proteins having their native amino acid sequences. The enzyme reactions can be carried out in free solution, or the AAP can be immobilized on a solid support, for reactions carried out in vitro. An efficient method for converting Ala-hGH to hGH, for example, comprises expression of Ala-hGH in E. coli, recovery of inclusion bodies, solubilization and refolding in detergent, detergent removal by ultrafiltration, selective precipitation, enzyme cleavage, followed by two column chromatography steps.

Abstract: The present invention provides compositions and methods for the treatment of reduced blood flow to the central nervous system in a subject. More particularly, the invention provides a combination therapy for the treatment of a central nervous system ischemic condition comprising the administration to a subject of an amphetamine in combination with a cyclooxygenase-2 selective inhibitor.

Abstract: The present invention is directed to a compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from the group consisting of H and methyl; and R2 is selected from the group consisting of H and methyl. The compounds possess useful nitric oxide synthetase inhibiting activity, and are expected to be useful in the treatment or prophylaxis of a disease or condition in which the synthesis or over synthesis of nitric oxide forms a contributory part.

Abstract: The invention relates to polycyclic aryl and heteroaryl substituted 1,4-quinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

Abstract: The present invention provides compositions and methods for the treatment of a vaso-occlusive event. More particularly, the invention provides a combination therapy for the treatment of a vaso-occlusive event comprising the administration to a subject of a selective serotonin reuptake inhibitor in combination with a cyclooxygenase-2 selective inhibitor.

Abstract: The invention relates to polycyclic aryl and heteroaryl substituted 4-pyridone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

Abstract: Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful for treatment of renal failure.

Abstract: The present invention provides compositions and methods for the treatment of herpes virus infections. In one aspect, the invention provides a combination therapy for treating a herpes virus infection comprising the administration to a subject of an anti-herpes virus agent in combination with a cyclooxygenase-2 selective inhibitor. In another aspect, the invention provides a mono therapy for treating a herpes virus infection comprising administering a cyclooxygenase-2 selective inhibitor to a subject.

Abstract: Pyrrolo[1,2-b][1,2,4]oxadiazine-2,3(6H)-diones having the formula: or pharmaceutically acceptable salts thereof, useful as nitric oxide synthase inhibitors wherein each substituent is defined herein.

Abstract: Compounds are described which inhibit mitogen activated protein kinase-activated protein kinase-2 (MK-2). Methods of making such compounds are described, as well as a method of using them for the inhibition of MK-2, and for the prevention or treatment of a disease or disorder that is mediated by TNF&agr;, where the method involves administering to the subject an MK-2 inhibiting compound of the present invention. Pharmaceutical compositions and kits which contain the present MK-2 inhibiting compounds are also described.

Abstract: Compositions and methods to treat or prevent pain, inflammation, or inflammation-related disorder, as well as a neurologic disorder involving neurodegrneration in a subject that is in need of such prevention or treatment involve a combination of a Cox-2 inhibitor and a 5-HT1A receptor modulator.

Abstract: Combinations of synthetic low molecular weight catalysts for the dismutation of superoxide and Nonsteroidal Analgesic/Anti-Inflammatory Drugs (NSAIDs) are potent analgesics that are effective in elevating the pain threshold in hyperalgesic conditions.

Abstract: The present invention is directed toward a composition comprising a compound isolated from Dysidea species sponges that is capable of inhibiting serine proteases of the coagulation cascade. In particular, this composition inhibits the TF/VIIa complex of the coagulation cascade. The invention is also directed toward methods employing this composition as a part of anticoagulant therapy.

Abstract: Aminocyanopyridine compounds are described which can inhibit mitogen activated protein kinase-activated protein kinase-2. Pharmaceutical compositions and kits that contain these compounds are also described.

Abstract: Methods of treating cyclooxygenase-2 mediated disorders comprising administering to a subject a therapeutically effective amount of one or more fluoro-substituted benzenesulfonyl compounds corresponding to Formula I: 1

Abstract: The present invention provides compositions and methods for the treatment or prevention of Alzheimer's disease. More particularly, the invention provides a combination therapy for the treatment or prevention of Alzheimer's disease, wherein the therapy comprises administering to a subject an amyloid beta vaccine in combination with a cyclooxygenase-2 selective inhibitor.

Abstract: The invention relates to polycyclic aryl and heteroaryl substituted benzene compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

Abstract: A method is described for inhibiting mitogen activated protein kinase-activated protein kinase-2 in a subject in need of such inhibition, where the method involves administering to the subject an anminocyanopyridine MK-2 inhibiting compound, or a pharmaceutically acceptable salt thereof.

Abstract: Aminocyanopyridine compounds are described which are capable of inhibiting mitogen activated protein kinase-activated protein kinase-2. Pharmaceutical compositions and kits are also described, which include an anminocyanopyridine MK-2 inhibiting compound.

Abstract: A method of making aminocyanopyridine compounds which are capable of inhibiting mitogen activated protein kinase-activated protein kinase-2 is described.