124 results about "Non peptide" patented technology

Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-alpha from membrane bound TNF-alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having the formulawherein R2 and R3 form a heterocyclic ring and A is S, S(O), or S(O)2, and R1 and R4 are defined herein.

Disclosed are a protein conjugate with improved in vivo duration and stability and the use thereof. The protein conjugate includes a physiologically active polypeptide, a non-peptide polymer and an immunoglobulin Fc fragment. Since the three components are covalently linked, the protein conjugate has extended in vivo duration and enhanced stability for the physiologically active polypeptide. The protein conjugate maintains the in vivo activity at relatively high levels and remarkably increases the serum half-life for the physiologically active polypeptide, with less risk of inducing undesirable immune responses. Thus, the protein conjugate is useful for developing long-acting formulations of various polypeptide drugs.

Disclosed are an Fc fragment modified by a non-peptide polymer, a pharmaceutical composition comprising the Fc fragment modified by the non-peptide polymer as a carrier, a complex of the Fc fragment and a drug via a linker and a pharmaceutical composition comprising such a complex. The Fc fragment modified by a non-peptide peptide according to the present invention lacks immunogenicity and effector functions. Due to these properties, the Fc fragment maintains the in vivo activity of a drug conjugated thereto in high levels, remarkably increases the serum half-life of the drug, and remarkably reduces the risk of inducing immune responses.

The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and an immunoglobulin Fc region, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

Drug-containing nanoparticles are provided that enable effective targeting and sustained-release of a water-soluble, non-peptide, low-molecular weight drug and cause reduced accumulation of the drug in the liver. The nanoparticles containing a water-soluble, non-peptide, low-molecular weight drug are obtained by hydrophobicizing the water-soluble, non-peptide, low-molecular weight drug by a metal ion, and reacting the hydrophobicized drug with a poly(lactic acid)-polyethylene glycol block copolymer or a poly(lactic-co-glycolic acid)-polyethylene glycol block copolymer. The nanoparticles have favorable targeting and sustained-release properties and cause reduced accumulation of the drug in the liver.

Invented is a method of treating degenerative diseases / injuries, in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

The present invention provides a method for identifying inhibitors of protein kinases. Methods are also provided for inhibiting protein kinase activity. Specific non-peptide protein tyrosine kinase inhibitor are provided. The protein kinases produced using the method of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, or immune system activity.

Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are described. Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intermediates useful in their preparation are also described.

The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and a carrier substance, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

Compounds are provided which are crossreactive with peptides such as those which bind G-protein-linked receptors, together with preparative and therapeutic methods therefor. The compounds have the general structure:wherein at least one of R1, R2, R3, R4, or R5 comprises a functional group which is chemically similar to that found in the peptide of interest.

Disclosed is a novel long-acting glucagon conjugate in which glucagon or its derivative is covalently linked to a polymer carrier via a non-peptide linker, and a pharmaceutical composition comprising the same as an effective ingredient useful for the prevention and treatment of obesity. Since the long-acting glucagon conjugate of the present invention shows improved in vivo durability and stability, when used in combination with an anti-obesity drug, it is possible to induce synergistic effects on the loss of body weight and decrease in food intake without causing any side-effects such as fluctuation in blood glucose level. Accordingly, the long-acting peptide conjugate of the present invention is very effective for the prevention and treatment of obesity.

The invention provides methods, oral care products and kits for treating mouth tissues of an animal. In particular, the invention provides methods, oral care products and kits which use or comprise a non-peptide polyamine chelating agent, most preferably trientine, or a physiologically-acceptable salt thereof, which can inhibit the release of pro-inflammatory cytokines, particularly interleukin 8, from cells located in tissues of the mouth and can reduce the damage done by reactive oxygen species (ROS) to such tissues.

The present invention provides a method for identifying inhibitors of protein kinases and / or protein phosphatases. Methods are also provided for inhibiting protein kinase and / or protein phosphatase activity. Specific non-peptide protein tyrosine kinase and / or protein phosphatase inhibitors are provided. The protein kinase or protein phosphatase inhibitors of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, immune system activity, Type II diabetes, and obesity.

A delivery device for and method of modulating a condition relating to sodal cognition and / or behaviour in a human subject using oxytocin, non-peptide agonists thereof and / or antagonists thereof, comprising: providing a nosepiece to a first nasal cavity of the subject; and providing a supply unit for administering less than 24 IU of oxytocin, non-peptide agonists thereof and / or antagonists thereof through the nosepiece to an upper region posterior of the nasal valve which is innervated by the trigeminal nerve.

The invention concerns methods and means for facilitating the translocation of molecules through the gastrointestinal tract of mammals. In particular, the invention concerns methods for identifying antibodies, including antibody fragments, capable of translocation from the lumenal side of gastrointestinal tissue into the blood stream or into the lymphatic circulation. The invention further concerns the identification of sequences within or associated with such antibodies facilitating translocation through the gastrointestinal tract. The invention additionally concerns the use of such antibodies and sequences, or other molecules or moieties identified by using such antibodies or sequences, for facilitating oral delivery and absorption of molecules, such as biomolecules (including proteins and nucleic acids), antibodies, peptides, and non-peptide small molecules.

The testing of tumor cells, including human tumors capable of metastases, in assays employing fibronectin-depleted substrates is described. Ex vivo induction of cells, including biopsied human cells, is performed with invasion-inducing agents. Additionally, anti-cancer chemotherapeutics are described. Specifically, chemotherapeutic agents which have anti-metastatic and anti-growth properties are described including non-peptide compositions of matter.

The in vitro polymerization of silica, silicone, non-silicon metalloid-oxane and metallo-oxane polymer networks, by combining a catalyst and a substrate to polymerize the substrate to form silica, polysiloxanes, polymetalloid-oxanes polymetallo-oxanes (metal oxides), polyorganometalloid oxanes, polyorganometallo oxanes, and the polyhydrido derivatives thereof, at about neutral pH. The nanostructure-directing catalysts have a nucleophilic functionality and a hydrogen-bonding acceptor group, and include: silicateins, enzymes that work by a mechanism functionally related to that of the silicateins; self-assembling peptides related to those synthesized and demonstrated capable of acting as biomimetic substitutes for the silicateins; non-peptide-based synthetic polymers containing a nucleophilic group and a hydrogen bonding amine such that the polymer functions by a mechanism of action related to that of the silicateins; materials having such chemical functionality as a nucleophilic group and or a hydrogen bonding amine which, acting in concert with nanoconfinement and or chemical functionality of the surface or matrix to which the functionality is attached, acts catalytically by a mechanism related to that of the silicateins; and small-molecule non-polymeric biomimetic catalysts that operate by the same mechanism as silicateins. The substrate is selected from groups consisting of silicon alkoxides, non-silicon metalloid alkoxides or metal alkoxides, and any organic, organometallic or hydrido derivatives of the foregoing; inorganic and organic oxygen-containing chelates of silicon, non-silicon metalloids or metals and any organic, organometallic or hydrido derivatives of the foregoing; and inorganic and organic esters of the hydoxides of silicon, non-silicon metalloids or metals and any organic, organometallic or hydrido derivatives of the foregoing; and inorganic and organic hydolyzable salts, complexes or conjugates of the hydroxides of silicon, non-silicon metalloids or metals and any organic, organometallic and hydrido derivates of the foregoing.

The present invention relates to small molecule antagonists of Bcl-2 family proteins such as Bcl-2 and / or Bcl-XL. In particular, the present invention provides non-peptide cell permeable small molecules (e.g., tricyclo-dibenzo-diazocine-dioxides) that bind to a pocket in Bcl-2 / Bcl-XL that block the anti-apoptotic function of these proteins in cancer cells and tumor tissues exhibiting Bcl-2 protein overexpression. In preferred embodiments, the small molecules of the present invention are active at the BH3 binding pocket of Bcl-2 family proteins (e.g., Bcl-2, Bcl-XL, and Mcl-1). The compositions and methods of the present invention are useful therapeutics for cancerous diseases either alone or in combination with chemotherapeutic or other drugs.

Osteoporosis and the like metabolic bone diseases have a high frequency of causing lumbago and the like pains and bone fracture, due to lowering of the bone strength caused by the reduction of bone mass. Accordingly, great concern has been directed toward the creation of a drug which can increase the bone mass and bone strength by controlling the whole bone metabolism. The pharmaceutical composition or combination product of the invention comprising a non-living body-derived non-peptide osteoblast differentiation promoting compound and a bisphosphonate having a bone resorption inhibitory action is useful as a bone mass increasing inducer which can increase the bone mass and / or bone strength by controlling the bone metabolism.

Modulating agents for inhibiting or enhancing desmosomal cadherin mediated cell adhesion are provided. The modulating agents comprise one or more of: (a) a peptide sequence that is at least 50% identical to a desmosomal cadherin CAR sequence; (b) a non-peptide mimetic of a desmosomal cadherin CAR sequence; (c) a substance, such as an antibody or antigen-binding fragment thereof, that specifically binds a desmosomal cadherin CAR sequence; and / or (d) a polynucleotide encoding a polypeptide that comprises a desmosomal cadherin CAR sequence or analogue thereof. Methods for using such modulating agents for modulating desmosomal cadherin-mediated cell adhesion in a variety of contexts are also provided.

This invention relates to macrocyclic chelants comprised of one or two heteroatom-containing bridges, compositions containing them and their use in medicine, particularly in diagnostic imaging and radiotherapy. This invention relates especially to the use of metal chelates of the macrocyclic chelants as metallopharmaceuticals in Magnetic Resonance Imaging (MRI) and radiopharmaceuticals. This invention also relates to macrocyclic chelants as bifunctional chelating agents (BFC's) for the labeling of biologically active targeting molecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands, with metal ions and radioisotopes.

The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and an immunoglobulin Fc region, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

Invented are non-peptide TPO mimetics. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.

Compounds of Formula I or II, and methods of making and using thereof, are described herein.M represents a macrolide subunit,E is a C1-6 group, optionally containing one or more heteroatoms,D is an alkyl or aryl group,A is a linking group connected to D,B is an alkyl, alkylaryl or alkylheteroaryl spacer group,ZBG is a Zinc Binding Group,R1, R2 and R4 are independently are selected from hydrogen, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkanoate group, a C2-6 carbamate group, a C2-6 carbonate group, a C2-6 carbamate group, or a C2-6 thiocarbamate group,R3 is hydrogen or —OR5,R5 is selected from a group consisting of Hydrogen, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, C1-6 alkanoate group, C2-6 carbamate group, C2-6 carbonate group, C2-6 carbamate group, or C2-6 thiocarbamate group.

Non-peptide compounds of formula (I) having activity as specific antagonists of bradykinin (BK) B2 receptor. The compounds are chemically characterized by the presence of an alpha, alpha-disubstituted amino acid at least one amino group, free or salified, or the corresponding ammonium quaternary salt. These BK receptor antagonists are a novel class of medicaments which can be used in all the disorders in which said receptors are involved

A cell population expressing folate receptors is selectively targeted with a non-peptide folic acid analogue. The non-peptide folic acid analogue is conjugated to a diagnostic or therapeutic agent to enable selective delivery of the agent to the targeted cell population.

Invented is a method for the preservation of human platelet lifespan and / or efficacy during storage which comprises the addition of an effective amount of a non-peptide TPO receptor agonists to a storage solution containing human platelets.

Invented is a method of treating degenerative diseases / injuries, in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

Invented is a method of treating degenerative diseases / injuries, in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

Disclosed herein is a species of peptide and non-peptide inhibitors of Akt, an oncogenic protein. Beginning with a residue of Akt target substrate GSK-3, the functional domains of the GSK-3 residue were characterized. Functionally homologous non-peptide groups were substituted for the amino acids of the GSK-3 creating a hybrid peptide-non-peptide and non-peptide compounds capable of binding to Akt. The non-peptide compounds show increased stability and rigidity compared to peptide counterparts and are less susceptible to degradation. The bound non-peptide compounds exhibit an inhibitory effect on Akt, similar to peptide-based Akt inhibitors.