301 results about "Activating receptors" patented technology

Using betaKlotho or a substance that increases or inhibits betaKlotho activity as an agent for controlling the activity of FGF21 mediated by an FGF receptor, the present invention provides a pharmaceutical composition comprising such betaKlotho or such substance as an active ingredient, particularly, a pharmaceutical composition for anti-metabolic syndrome, and further particularly, a pharmaceutical composition for therapeutic or preventive use associated with the control of blood glucose level. In addition, the present invention provides a screening system for each of a substance that enhances or suppresses betaKlotho activity, an FGF21-like active substance, and a betaKlotho-like active substance, which uses a cell system that has expressed an FGF receptor and / or betaKlotho on the surface thereof.

The present invention relates to novel ether compounds, compositions comprising ether compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising an ether compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

Methods and compositions are provided for protecting or enhancing excitable tissue function in mammals by systemic administration of an erythropoietin receptor activity modulator, such as erythropoietin, which signals via an EPO-activated receptor to modulate the function of excitable tissue. Excitable tissues include central neuronal tissues, such as the brain, peripheral neuronal tissues, retina, and heart tissue. Protection of excitable tissues provides treatment of hypoxia, seizure disorders, neurodegenerative diseases, hypoglycemia, and neurotoxin poisoning. Enhancement of function is useful in learning and memory. The invention is also directed to compositions and methods for facilitating the transport of molecules across endothelial cell tight junction barriers, such as the blood-brain barrier, by association of molecules with an erythropoietin receptor activity modulator, such as an erythropoietin.

This invention relates to a subcutaneous deliverable composition containing an agonist of the peroxisome proliferator-activated receptor-gamma, and a method for treating facial skin defects in a mammalian subject using the subcutaneous deliverable composition.

The present invention relates to novel ether compounds, compositions comprising ether compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising an ether compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

The present invention relates to compounds and methods useful as modulators of Peroxisome Proliferator-Activated Receptors (PPARs) for treatment or prevention of disease.

The invention relates to the discovery that farnesoid X receptor (FXR) agonists can be used in combination with peroxisome proliferation activated receptor gamma (PPARγ) agonists to reduce drug-induced adverse side effects in patients suffering from conditions such as insulin resistance, Type II diabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and heart disease. Particularly, the present invention encompasses methods for treating patients suffering from drug-induced adverse side effects with selective PPARγ, dual PPARα / γ and pan PPARα / γ / δ agonists in combination with FXR agonists.

Novel activating receptors of the lg super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Salts and polymorphs of a compound useful in the treatment of inflammatory and metabolic conditions and diseases are provided herein. In particular, the invention provides salts and polymorphs of a compound which modulates the expression and / or function of a peroxisome proliferator-activated receptor. The salts and polymorphs are useful for the treatment or prevention of conditions and disorders associated with energy homeostasis such as type II diabetes, lipid metabolism, adipocyte differentiation and inflammation.

The present invention relates to bispecific molecules that are immunoreactive to an activating receptor of a companion animal immune effector cell and to B7-H3, and to the use of such bispecific molecules in the treatment of cancer in companion animals.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Novel fusion proteins that comprise a first portion that corresponds to an antibody-like protein that is specific for an activating receptor on an effector lymphocyte or a variant thereof and a second portion that corresponds to a portion of a cell membrane protein and that binds to a cell-associated target are provided, as are methods of producing such fusion proteins, uses and methods involving such fusion proteins, and compounds and compositions related to such fusion proteins.

A method of increasing the insulin sensitivity of insulin resistant cells includes administering to the cells an amount of all-trans-retinoic acid effective to activate transcription factor perosixome proliferator-activated receptor (PPAR) β / δ of the cells.

The present invention relates to novel sulfoxide and bis-sulfoxide compounds, compositions comprising sulfoxide and bis-sulfoxide compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising an ether compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

A compound of formula (I): (wherein R1-R10 are each independently hydrogen, halogen, optionally substituted lower alkyl or the like, X1 is —O—, —S—, —NR11— (wherein R11 is hydrogen, lower alkyl or the like), —CR12R13CO—, —(CR12R13)mO—, —O(CR12R13)m- (wherein R12 and R13 are each independently hydrogen or lower alkyl and m is a integer between 1 and 3) or the like, X2 is a bond, —O—, —S—, —NR14— (wherein R14 is hydrogen, lower alkyl or the like, R14 and R6 can be taken together with the neighboring atom to form a ring) or —CR15R16— (wherein R15 and R16 are each independently hydrogen or lower alkyl, R15 and R6 or R10 can be taken together with the neighboring carbon atom to form a ring, R16 and R9 can be joined together to form a bond), X3 is COOR17, C(═NR17)NR18OR19 or the like), a pharmaceutically acceptable salt or a solvate thereof.

The present invention relates to novel ketone compounds, compositions comprising ketone compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising a ketone compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

The invention relates to novel mammalian perixosome proliferator-activated receptor (PPAR) poplypeptides and their use. In a particular embodiment, PPAR polypeptides with mutations in the P-box domain possess advantageous properties as transcriptional activators for PPRE-bearing expression vectors and expression systems. The invention includes PPAR polypeptides, nucleic acids encoding them, expression systems, vectors, and methods for inducibly expressing a gene of interest. The methods and expression systems of the invetion provide improved dose-response or inducibility characteristics, improved and / or altered effects on cellular PPAR function, and / or improved transcriptional control. The selection of a homologous PPAR polypeptide to prepare the novel PPAR polypeptide of the invetion for a cell or tissue also improves the immune reaction side effect potential for particular uses.

The present invention easily and efficiently provides a peroxisome proliferator-activated receptor ligand, and a composition for amelioration of insulin resistance or for prevention and / or amelioration of the insulin resistance syndrome containing the same, as an active ingredient. The present invention relates to a peroxisome proliferator-activated receptor ligand which comprises a prenylflavonoid, a chalcone derivative exclusive of prenyl flavonoids, a flavonol derivative exclusive of prenylflavonoids, and a salt, a glycoside and / or an esterified substance thereof acceptable as a pharmaceutical preparation or a food or a beverage; a composition containing the above ligand; a plant-derived extract containing the above ligand; and a process for producing the above extract.

Analogs of SRIF which are selective for SSTR4 in contrast to the other cloned SRIF receptors are useful in determining tissue and cellular expression of the receptor SSTR4 and its biological role in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,4,5,12,13[Ala7]-SRIF; des-AA1,2,4,5,12,13[Aph7]-SRIF, des-AA1,2,4,5,12,13[Aph7]Cbm-SRIF; des-AA1,2,4,5,12,13[Tyr2,Ala7]-Cbm-SRIF, and des-AA1,2,4,5,12,13[Tyr7,CβMe-L-2Nal8]-SRIF, and counterparts incorporating D-Cys3 and / or D-Trp8 and / or Ala11, bind with high affinity to the cloned human receptor SSTR4 and activate the receptor, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR3 or SSTR5. By incorporating an iodinated tyrosine in position-2 in these SSTR4-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, cytotoxins or highly radioactive elements can be N-terminally coupled or complexed thereto.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-beta. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

The invention provides novel substituted benzylthiazolidine-2,4-dione derivatives that bind to receptor to activate as ligands of human peroxisome proliferator-activated receptor (PPAR) and exhibit blood glucose-decreasing action and lipid-decreasing action, and processes for preparing them.It relates to substituted benzylthiazolidine-2,4-dione derivatives represented by the general formula (1)[wherein the bond mode of A denotes -CH2CONH-, -NHCONH-, -CH2CH2CO- or -NHCOCH2-, and B denotes a lower alkyl group with carbon atoms of 1 to 4, lower alkoxy group with carbon atoms of 1 to 3, halogen atom, trifluoromethyl group, trifluoromethoxy group, phenyl group which is unsubstituted or may have substituents, phenoxy group which is unsubstituted or may have substituents or benzyloxy group which is unsubstituted or may have substituents], their medicinally acceptable salts, their hydrates and processes for preparing them.

Novel compounds of the general formula (I), the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and / or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

The invention provides a method for efficiently preparing an NK cell, which can improve the multiplication rate and the purity of the NK cell through combination of stimulation effects of cell factors and feeder cells. The method is mainly characterized by comprising the steps as follows: NCR3LG1 and m IL-15 are transfected to a K562 cell simultaneously, m IL-15 can be used for adjusting activation and multiplication of the NK cell, NCR3LG1 serving as a ligand of NKp30 which is one of main activated receptors on the surface of the NK cell can effectively stimulate activation of the NK cell, and NCR3LG1 and m IL-15 have a synergistic effect; and PBMC(peripheral blood mononuclear cells) can be multiplied over 500 times in 21 cultivation days through stimulation of factors of freely added IL-2, IL-21 and the like, and a proportion of CD3-CD56+NK cell exceeds 70%; and up to now, a research report that NCR3LG1 and m IL-15 are transfected to the feeder cells simultaneously and jointly stimulate and activate the NK cell in combination of free cell factors is absent. The invention firstly provides a method for jointly cultivating and preparing the NK cell in combination of the feeder cells and the free factors.

This invention provides for a fusion protein between an IL2αβγ Selective Agonist protein (IL2 Selective Agonist) and a IgG Fc protein. The IL2 Selective Agonist moiety provides a therapeutic activity by selectively activating the IL2αβγ form of the receptor, thus selectively stimulating Tregs. The Fc moiety provides a prolonged circulating half-life compared to the circulating half-life of IL-2 or an IL2SA protein.

The invention provides novel substituted phenylpropanoic acid derivatives that activate by binding to receptor as ligands of human peroxisome preliferant-activated receptor alpha (PPARalpha), and exhibit potent decreasing action on lipids in blood (cholesterol and triglyceride).It relates to a substituted phenylpropanoic acid derivatives represented by a general formula (1),their pharmaceutically acceptable salts and their hydrates, and processes for preparing them.