Abstract: Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: wherein R1, R2, R3, R4, R5 and R6 are as described herein.

Abstract: The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of USP30, and the treatment of USP30-mediated disorders.

Abstract: Sinusitis and other disorders of the ear, nose and throat are diagnosed and/or treated using minimally invasive approaches with flexible or rigid instruments. Various methods and devices are used for remodeling or changing the shape, size or configuration of a sinus ostium or duct or other anatomical structure in the ear, nose or throat; implanting a device, cells or tissues; removing matter from the ear, nose or throat; delivering diagnostic or therapeutic substances or performing other diagnostic or therapeutic procedures. Introducing devices (e.g., guide catheters, tubes, guidewires, elongate probes, other elongate members) may be used to facilitate insertion of working devices (e.g. catheters e.g. balloon catheters, guidewires, tissue cutting or remodeling devices, devices for implanting elements like stents, electrosurgical devices, energy emitting devices, devices for delivering diagnostic or therapeutic agents, substance delivery implants, scopes etc.

Abstract: The present disclosure related to an oral composition, and more particularly, to an oral composition for reducing tooth sensitivity. More specifically, the oral composition contains zinc and a copper salt capable of occluding dental tubules by agglomerating proteins, contributing to the reduction effect of tooth sensitivity, and to maintain this, allows a water soluble or alcohol soluble polymer to coat the dental tubules and be maintained for a long time, thereby solving the main cause of tooth sensitivity, as a result, providing an effect on the prevention or reduction of symptoms of tooth sensitivity in a short time.

Abstract: Fragments of ARS-interacting multi-functional protein 1 (AIMP1) protein and a composition comprising the same as an active ingredient for preventing skin-aging, anti-wrinkle, and improving skin flexibility or elasticity are described.

Abstract: Pentacyclic triterpene weight loss agents are provided herein. Also provided are pharmaceutical formulations containing a therapeutically effective amount of one or more of the weight loss agents, or pharmaceutically acceptable salts or prodrugs thereof, in combination with one or more pharmaceutically acceptable excipients. The pharmaceutical formulations can be administered to a pre-obese, obese, or morbidly obese patient to induce weight loss, reduce body fat, reduce food intake, improve glucose homeostasis, prevent obesity, or a combination thereof. The weight loss agents can also be co-administered with leptin or a leptin analog.

Abstract: The present invention provides means and methods for selectively detecting activated MALT1 in a sample. Moreover, the present invention provides a method for diagnosing diseases, which are characterized by an increased MALT1 activity. Finally, the present invention provides methods for identifying patients which are amenable to treatment with a therapeutic agent capable of inhibiting MALT1 activity.

Abstract: The present invention relates to a therapeutic agent for amniotic fluid embolism (AFE). Furthermore, the present invention relates to a therapeutic agent for AFE comprising a C1-inhibitor, particularly a human plasma-derived C1-inhibitor.

Abstract: Embodiments are directed to compositions and methods of treating migraine and related neurological disorders. In certain aspects, methods and compositions are for reducing cortical spreading depression and/or suppressing the neurochemical basis for chronic and acute migraine events, and provide methods and pharmaceutical compositions related to both acute and preventive therapies for migraine events and related headaches.

Abstract: A water-in-oil emulsion comprising less than 60% water, and wherein said emulsion comprises an oil phase and a water phase, and wherein the water phase comprises a dipeptide selected from the group consisting of acetyl dipeptide (1) cetyl ester, acetyl dipeptide (3) aminohexanoate, azelaoyl bisdipeptide (10), coumaroyl dipeptide (3), dicetyl dipeptide (9), dipeptide diamino butyroyl benzylamide diacetate, dipeptide (1), dipeptide (10), dipeptide (11), dipeptide (12), dipeptide (15), dipeptide (16), dipeptide (17), dipeptide (18), dipeptide (19), dipeptide (2), dipeptide (20), dipeptide (3), dipeptide (4), dipeptide (5), dipeptide (6), dipeptide (7), dipeptide (8), dipeptide (8) HCL, dipeptide (9), hexanoyl dipeptide (3) norleucine acetate, methyl undecylenoyl dipeptide (16), nicotinoyl dipeptide (22), nicotinoyl dipeptide (23), nicotinoyl dipeptide (24), nicotinoyl dipeptide (26), oleoyl dipeptide (15), palmitoyl dipeptide (10), palmitoyl dipeptide (13), palmitoyl dipeptidel (7), palmitoyl dipeptide (5) diami

Abstract: The present invention provides an inhibitor of an ADAMTS proteoglycanase for use in treating or preventing cardiac remodeling or for use in treating or preventing heart failure in a subject. In particular, the present invention provides an inhibitor of ADAMTS4 or ADAMTS5 for use in treating or preventing cardiac remodeling or chronic heart failure in a subject with cardiac remodeling or with chronic heart failure, or with a condition that may lead to cardiac remodeling and/or chronic heart failure. Also provided is a method of treating or preventing cardiac remodeling or treating or preventing heart failure which method comprises administering to a subject in need thereof a therapeutically effective amount of an inhibitor of an ADAMTS proteoglycanase. Also provided is the use of an inhibitor of an ADAMTS proteoglycanase in the manufacture of a medicament for treating or preventing cardiac remodeling or treating or preventing heart failure.

Abstract: Pentacyclic triterpene weight loss agents are provided herein. Also provided are pharmaceutical formulations containing a therapeutically effective amount of one or more of the weight loss agents, or pharmaceutically acceptable salts or prodrugs thereof, in combination with one or more pharmaceutically acceptable excipients. The pharmaceutical formulations can be administered to a pre-obese, obese, or morbidly obese patient to induce weight loss, reduce body fat, reduce food intake, improve glucose homeostasis, prevent obesity, or a combination thereof. The weight loss agents can also be co-administered with leptin or a leptin analog.

Abstract: The present invention relates to a novel cyanopyrimidine compound and a pharmaceutical composition which have a safe and potent adenosine A2a receptor agonistic activity.

Abstract: The present invention relates to a method of directing in situ oriented immobilization of a protein on a support. This method involves providing a support and contacting the support with a solution. The solution comprises (a) a protein comprising a coupling moiety and (b) a molecule comprising a first group reactive with the support and a second group reactive with the coupling moiety. The molecule binds (i) the support at the first group and (ii) the coupling moiety at the second group, thereby immobilizing and orienting, in situ, the protein on the support. Also described are a protein array and a method of screening compounds for protein interaction.

Abstract: The present application relates to novel fluorinated epoxyketone-based compounds, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions mediated by proteasome inhibition, in particular, the present application includes compounds of Formula I, and compositions and uses thereof.

Abstract: Various embodiments provide methods and related compositions for increasing the population size of hematopoietic stem cells (HSCs) in patients that may benefit from reconstitution of stem cells and/or differentiated cells of the blood lineage. The present methods enable the production of HSCs ex vivo and in vivo by reducing latexin expression and/or latexin activity within HSC exposed to various antagonists. Inhibition of latexin expression and/or latexin activity by various antagonists can promote HSC proliferation and/or inhibit HSC apoptosis. Antagonists that can reduce latexin expression and/or latexin activity can be utilized to regenerate endogenous HSCs within patients affected with disorders, diseases, cancers, or therapies for such conditions, that result in the depletion or reduction in HSCs.

Abstract: Methods for inhibiting activated protein C (APC) comprising contacting the APC with a Kunitz polypeptide in an amount effective in inhibiting the activity of APC, wherein the Kunitz polypeptide comprises six cysteine residues at positions corresponding to positions 7, 16, 32, 40, 53, and 57 in SEQ ID NO:1, a motif X1GX2CBX? at positions corresponding to positions 13-18 in SEQ ID NO:1, wherein each of X1 and X2, independently, is any amino acid residue, B is a basic amino acid residue, and X? is G, A, or V; and at least one heparin-binding motif, which can present at the C-terminus of the Kunitz polypeptide.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the small molecule drug not attached to the water-soluble oligomer.

Abstract: A method and composition for treating or preventing antibody-mediated rejection (AMR) of a transplanted organ are provided.

Abstract: The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions. This invention also relates to methods for the preparation of amino acid keto-epoxides. Specifically, allylic ketones are stereoselectively converted to the desired keto epoxides.

Abstract: The invention relates to an in vitro method for prognosis, diagnosis or determination of the evolution of a condition involving an altered production of Basic Proline-rich Lacrimal Protein (BPLP) or of any of its maturation products, by detecting, or quantifying in a biological sample of a test subject, a BPLP protein or a maturation product thereof, and comparing the production of BPLP protein or maturation product with the production of the same in a biological sample of a control subject

Abstract: The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGF?). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

Abstract: The present invention relates to modified opiorphin peptides as new inhibitors of metallo-ectopeptidases.

Abstract: Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.

Abstract: Polymer conjugates containing a C1-inhibitor having at least one substantially non-antigenic polymer covalently attached to the C1-inhibitor via glycan group of the C1 inhibitor is provided. In addition, methods of making the conjugates as well as methods of treatment using the conjugate of the present invention are also provided.

Abstract: A wound dressing material for controlled activation of a wound healing therapeutic compound in the presence of a protease enzyme in a wound fluid, the material comprising: a medically acceptable polymer; a wound healing therapeutic agent; an inhibitor of the protease enzyme; and a linker group which is cleavable by the protease enzyme, wherein the activities of both the wound healing therapeutic agent and the inhibitor are increased by contacting the wound dressing material with a wound fluid containing the protease enzyme. For example, the enzyme may be a matrix metalloproteinase, the therapeutic agent may be a reactive oxygen scavenger, and the inhibitor may be a tissue inhibitor of metalloproteinase (TIMP).

Abstract: The disclosure relates to compounds, peptides or peptidomimetics that inhibit, reduce or prevent protease activity and the use of these compounds, peptides or peptidomimetics to treat or prevent a condition. In particular the condition may be periodontal disease. The protease activity may be activity of a gingipain. The compounds, peptides or peptidomimetics of the invention may also be used in assays for the identification of protease inhibitors.

Abstract: The present disclosure serves to reduce the healing time of tissue wounds, including those formed during surgery, whether necessary or elective (including cosmetic surgery), by providing a therapeutic dose of a pancreatic enzyme inhibitor.

Abstract: Method for preparing an oxidized polysaccharide-protein composition, by (a) oxidizing a polysaccharide with an oxidizing agent to form an oxidized polysaccharide where less than 20% of the oxidized units are comprised of alpha-hydroxy aldehyde units, (b) reacting the oxidized polysaccharide with a protein to form a composition comprising an oxidized polysaccharide-protein conjugate, and (c) maintaining the oxidized polysaccharide-protein conjugate composition by placing it in an environment where the temperature is less than 8° C. The oxidized polysaccharide and the protein are conjugated via one or more imine bonds, the oxidized polysaccharide-protein composition is soluble in aqueous solvent, and the composition is capable of releasing the protein.

Abstract: In particular, in alternative embodiments, the invention provides pharmaceutical compounds and formulations comprising a family of epoxyketone compounds, which include racemic mixtures or racemates, isomers, stereoisomers, diastereoisomers, derivatives and analogs, and methods for making and using them. In alternative embodiments, pharmaceutical compositions and formulations of the invention are administered to an individual in need thereof in an amount sufficient to treat, prevent, reverse and/or ameliorate an infection, disease or condition that can be ameliorated, treated, prevented or reversed by partially or completely inhibiting a chymotrypsin-like protease or a proteasome activity, including e.g.

Abstract: The invention provides peptide inhibitors of BACE1 that bind to the active site in a noncanonical fashion, and methods of use thereof.

Abstract: The present invention relates to compounds of Formula I, IA, II, HA, III, or IHA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

Abstract: The present invention relates to methods, pharmaceutical compositions and kits for use in the treatment of Adult T-cell leukemia/lymphoma. More particularly, the present invention relates to a combination of an interferon, an arsenic compound and a reverse transcriptase inhibitor for the treatment of Adult T-cell leukemia/lymphoma.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: The present invention relates to methods of treating dry eye using ?-turn peptidomimetic cyclic compounds or derivatives thereof. The ?-turn peptidomimetic cyclic compounds can be used alone, in combination and/or in conjunction with one or more other compounds, molecules or drugs that treat dry eye.

Abstract: The invention relates to compositions comprising (i) biocompatible hydrogel and (ii) one or more therapeutic agents contained within said hydrogel; wherein the hydrogel is cross-linked utilizing a cross-linker comprising a peptide sequence that is capable of being degraded by an enzyme; the therapeutic agent being effective as a treatment of a condition related to the presence of the enzyme.

Abstract: Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: wherein R1, R2, R3, R4, R5 and R6 are as described herein.

Abstract: The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGF?). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

Abstract: The invention provides nitrile-containing protease inhibitors caged to ruthenium compounds. The nitrile-caged ruthenium compounds provide inactivated inhibitors that can be delivered to surface or site for activation, for example, but exposure to light. The invention also provides methods for delivering protease inhibitors to subjects for the therapeutic treatment of conditions such as cancer.

Abstract: A method and composition for treating serotonin receptor-mediated conditions.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the small molecule drug not attached to the water-soluble oligomer.

Abstract: The present invention is directed to novel compounds of formula I and pharmaceutically acceptable salts, enantiomers thereof having inhibiting properties of dipeptidyl peptidase IV enzyme (DP-IV inhibitors). The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds along with its composition in the prevention or treatment of diseases associated with DP-IV enzyme.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

Abstract: The present invention relates to a proteinaceous construct comprising plasmatic or recombinant factor VIIa (FVIIa) or biologically active derivatives thereof, which are bound to a carbohydrate moiety comprising 1-4 sialic acid units, wherein the in vivo half-life of the proteinaceous construct is substantially prolonged in the blood of a mammal, as compared to the in vivo half-life of a FVIIa molecule not bound to a carbohydrate moiety. The invention also provides a method for controlling bleeding in a mammal having a bleeding disorder due to functional defects or deficiencies of FVIIa, FVIII, or FIX. The invention also provides a method for controlling bleeding in a mammal during surgery or trauma.

Abstract: Methods and compositions for treating patients (e.g., patients who are insulin resistant, patients who have diabetes, or are at risk for developing diabetes) are disclosed herein. The methods can include administration of an a1 antitrypsin (AAT) polypeptide or an agent, such as a nucleic acid molecule or organic compound, that promotes the expression or activity of a1-antitrypsin.

Abstract: The subject matter of the present invention is in particular the use of an amino acid sequence of IDE, or of an analogue or fragment thereof, or of at least one nucleic acid sequence encoding this sequence, as a biomarker, or as an active agent, with regard to a dandruff condition of the scalp.

Abstract: The present invention is an inhibitor of the trypsin-like ?2/?2i sites of the proteasome. The inhibitor is characterized as being a peptide-based epoxyketone or vinyl sulfone that contains an arginine or 4-aminomethylene-L-phenylalanine at the C-terminus (i.e., at the P1 position). Methods for using the inhibitor to inhibit the activity of the ?2/?2i site of a proteasome and treat a proteasome-mediated disease or condition are also described.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The present invention relates to a method of treating cancer in a human and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering a proteasome inhibiting compound, and N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide, or a pharmaceutically acceptable salt thereof, and optional additional antineoplastic agents, to a human in need thereof.

Abstract: This invention relates to grassystatins A, B and C, and their isolated or purified forms. The compounds of the invention are useful as aspartic protease, gamma secretase, or metalloprotease inhibitors. Methods of using the compounds and compositions thereof are also disclosed.