166 results about "Fibroblast growth factor receptor" patented technology

Molecules comprising the antigen-binding portion of antibodies that block constitutive and / or ligand-dependent activation of a receptor protein tyrosine kinase, such as fibroblast growth factor receptor 3 (FGFR3), are found through screening methods, where a soluble dimeric form of a receptor protein tyrosine kinase is used as target for screening a library of antibody fragments displayed on the surface of bacteriophage. The molecules of the present invention which block constitutive activation can be administered to treat or inhibit skeletal dysplasia, craniosynostosis disorders, cell proliferative diseases or disorders, or tumor progression associated with the constitutive activation of a receptor protein tyrosine kinase.

A composition is provided that contains a polypeptide and a modulator or a cell comprising the polypeptide and a modulator, where the modulator specifically interferes with the activity of the polypeptide, and the polypeptide is either FGFR3 or FGFR4, inclusive of all polymorphic forms and variants thereof. The modulator can be an antibody or active fragments thereof, a small molecule drug, an RNAi molecule, an antisense molecule or a ribozyme. A method of treatment of tumors in a subject is also provided where an antagonist of FGFR3 or FGFR4 is administered to the subject.

Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma.

Described herein are inhibitors of FGFR, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of tyrosine kinases.

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

The present invention relates to a therapeutic agent represented by the General formula (I), or a pharmacologically acceptable salt thereof, or a solvate of the compound or the salt thereof:The therapeutic agent comprises a substance having the activity of inhibiting kinase activity of fibroblast growth factor receptor 2 (“FGFR2”). The therapeutic agent can be used for treating undifferentiated gastric cancer, and can also be used to treat organisms comprising a cell overexpressing FGFR2 or a cell expressing mutant FGFR2, or both. The present invention further relates to a pharmaceutical composition comprising an FGFR2 inhibitory and methods of treatment therewith. The present invention also relates to a method for predicting the effect of an FGFR2 inhibitory substance on a patient.

The present invention provides novel Fibroblast Growth Factor-like (FGF-like) polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, antibodies and methods for producing FGF-like polypeptides. Also provided for are methods for the diagnosis and treatment of diseases associated with FGF-like polypeptides.

Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.

The present invention relates to the identification of new proteins comprising fibroblast growth factor 21 (FGF21) and other metabolic regulators, including variants thereof, known to improve metabolic profiles in subjects to whom they are administered. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

The invention provides synthetic heparin-binding growth factor analogs of formulas I or II as given in the specification, having two peptide chains branched from a dipeptide branch moiety composed of at least one and preferably two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

A compound represented by formula (I) or a pharmacologically acceptable salt thereof, which can inhibit a fibroblast growth factor receptor (FGFR) family kinase in cancer tissues. (In the formula, A represents a 5- to 10-membered heteroaryl group, or a C6-10 aryl group; R1 and R2 independently represent H, OH, X, CN, NO2, a C1-4 haloalkyl group, a C1-6 alkyl group, or the like <R1 and R2 together form a (substituted) 3- to 10-membered heterocyclyl group or a (substituted) 5- to 10-membered heteroaryl group>; R3 represents H, a C1-5 alkyl group, a C6-10 aryl group, a C1-5 alkyl group, or a C1-4 haloalkyl group; and R4 represents H, X, a C1-3 alkyl group, a C1-4 haloalkyl group, OH, CN, NO2, or the like.)

The present invention provides a method of preventing and treating a T cell mediated disease, including inflammatory autoimmune diseases and in particular rheumatoid arthritis, by administering to an individual in need thereof at least one FGFR 3 inhibitor including a molecule comprising the antigen-binding portion of an antibody having a specific affinity for fibroblast growth factor receptor 3 (FGFR3), a FGFR3 specific small organic molecule tyrosine kinase inhibitor, a FGFR3 specific soluble receptor, a FGFR3 peptide or peptidomimetic, a FGFR3 specific RNA inhibitor, a FGFR3 specific antagonist ligand or a DNA vaccine encoding FGFR3 or a fragment thereof, or an inhibitor of heparan sulfate binding.

The present invention is directed toward a monoclonal antibody to fibroblast growth factor receptor 2, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.

The present invention relates to the use of Fibroblast Growth Factor Receptor I (FGFR1) extracellular domain (ECD) polypeptides for treatment of cancers characterized by ligand dependent activating mutations in Fibroblast Growth Factor Receptor 2 (FGFR2). For example, the present invention relates to the treatment of endometrial cancers and other cancers wherein tumor cells express FGFR2 mutants in the IgII-IgIII hinge region or IgIII domain of the protein, such as at amino acid positions 252 and / or 253.

The present invention relates to an isolated chimeric protein. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule. The present invention also relates to a pharmaceutical composition including an isolated chimeric protein and a pharmaceutically acceptable carrier. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule, and a pharmaceutically-acceptable carrier. Yet another aspect of the present invention relates to a method for treating a subject suffering from a disorder. This method includes selecting a subject suffering from the disorder and administering to the subject a therapeutically effective amount of a chimeric protein according to the present invention.

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

A process for detecting Mesenchymal Chondrosarcoma in a biological organism, comprising detecting, in a sample that contains Mesenchymal Chondrosarcoma cells obtained from a subject a first product indicative of elevated expression of a fibroblast growth factor receptor gene or a second product indicative of elevated amounts of a fibroblast growth factor receptor (FGFR-L1), wherein detection of said first or second product in elevated expression or amount, respectively, compared to a control sample containing normal or benign Mesenchymal Chondrosarcoma cells indicates the presence of Mesenchymal Chondrosarcoma in said subject. The sample is preferably obtained by a process comprising the steps of: (a) obtaining a tissue sample from a living biological organism, (b) disaggregating said tissue sample to produce disaggregated fragments of tissue sample whose maximum dimension is less than about 5 millimeters, wherein said tissue sample is disaggregated within about 10 minutes of the time said tissue sample is obtained from said biological organism, and (c) disposing said disaggregated tissue fragments in a sterile environment within a container, wherein said sterile environment is comprised of oxygen and a solution comprised of at least one cell type specific viability factor.

The present invention relates to the identification of new proteins comprising fibroblast growth factor 21 (FGF21) and other metabolic regulators, including variants thereof, known to improve metabolic profiles in subjects to whom they are administered. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

The invention belongs to the field of medicinal chemistry and particularly relates to 2,4,5-trisubstituted pyrimidine compounds taking FGFRs (fibroblast growth factor receptors) as targets as well as preparation methods and an application of the 2,4,5-trisubstituted pyrimidine compounds. The compounds can selectively inhibit phosphorylation of FGFR kinase so as to be used for treating malignant tumors closely related with the kinase, and can reduce adverse reactions; the compounds can be used for treating tumors related with the FGFR kinase or relevant diseases. The general formula of the 2,4,5-trisubstituted pyrimidine compounds is shown in the specification, wherein R<1>, R<2> and R<3> can be selected from multiple substituents and can be combined randomly. The 2,4,5-trisubstituted pyrimidine compounds taking the FGFRs as the targets have a good inhibition function on the FGFR1 kinase, have an anti-proliferation function on FGFR1-dependent tumor cell line KG1 cells, can be used for preparing antitumor drugs and have better antitumor effects.

The invention relates to a preparation method and application of an electrochemical sensor for achondroplasia prenatal diagnosis gene-fibroblast growth factor receptor 3 (FGFR3) gene polymorphism detection, belonging to the technical field of electrochemical detection. The preparation method is characterized by comprising the following steps: synthesizing a Hemin-MOFs composite material, reducing platinum nanoparticles onto the Hemin-MOFs composite material, and mixing a single-strand DNA signal probe with the composite material to obtain a biological signal probe; and carrying out layer-by-layer self-assembly by using reducible graphene oxide tetraethylenepentamine, nano gold and avidin to fix the biotinylated DNA capture probe, thereby preparing the electrochemical sensor for FGFR3-1138G>A gene polymorphism detection. The sensor is successfully used for detecting FGFR3-gene single base mutation. The sensor has the advantages of high sensitivity and high specificity, and is quick and convenient for detection. The invention provides a new detection method for prenatal noninvasive diagnosis of achondroplasia.

Isolated fibroblast growth factor receptor 5 (FGFR5) polypeptides are provided, together with polynucleotides encoding such polypeptides. Also provided are modulators of FGFR5 gene expression and binding molecules that specifically bind to, and agonize or antagonize, FGFR5 polypeptide finction. Binding molecules include antibodies, and functional fragments thereof, as well as scFv and Camelidae heavy chain IgG that specifically bind to FGFR5 thereby modulating the activity of FGFR5. Such binding agents and modulators of FGFR5 gene expression may be employed for the treatment of disorders including: osteopontin-mediated diseases; autoimmune diseases, such as systemic lupus erythematosus; bone disorders such as osteoporosis and osteopetrosis; and cancers, including cellular carcinomas such as hepatocellular carcinomas.

Isolated fibroblast growth factor receptor 5 (FGFR5) polypeptides are provided, together with polynucleotides encoding such polypeptides. Also provided are modulators of FGFR5 gene expression and binding molecules that specifically bind to, and agonize or antagonize, FGFR5 polypeptide function. Binding molecules include antibodies, and functional fragments thereof, as well as scFv and Camelidae heavy chain IgG that specifically bind to FGFR5 thereby modulating the activity of FGFR5. Such binding agents and modulators of FGFR5 gene expression may be employed for the treatment of disorders including: osteopontin-mediated diseases; autoimmune diseases, such as systemic lupus erythematosus; bone disorders such as osteoporosis and osteopetrosis; and cancers, including cellular carcinomas such as hepatocellular carcinomas.

Isolated fibroblast growth factor receptor 5 (FGFR5) polypeptides are provided, together with polynucleotides encoding such polypeptides. Also provided are modulators of FGFR5 gene expression and binding molecules that specifically bind to, and agonize or antagonize, FGFR5 polypeptide function. Binding molecules include antibodies, and functional fragments thereof, as well as scFv and Camelidae heavy chain IgG that specifically bind to FGFR5 thereby modulating the activity of FGFR5. Such binding agents and modulators of FGFR5 gene expression may be employed for the treatment of disorders including: osteopontin-mediated diseases; autoimmune diseases, such as systemic lupus erythematosus; bone disorders such as osteoporosis and osteopetrosis; and cancers, including cellular carcinomas such as hepatocellular carcinomas.

The present invention relates to general formula (I) spiroheterocyclic compound, its stereoisomer, enantiomer, tautomer or its mixture, or its pharmaceutically acceptable salt, solvate or prodrug, wherein ( II, k, j, P, Q, R1, R2 and R3) are as defined herein, which are useful for the treatment and / or prevention of diseases or conditions mediated by fibroblast growth factors and their receptor signaling pathways, such as cancer . Also disclosed are pharmaceutical compositions comprising the compounds and methods of using the compounds.

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

The invention belongs to the technical field of medicine, and specifically relates to the application of the following 11 compounds in the preparation of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor drugs: 3,5-bis(2,4-dichlorophenylene) Methyl)piperidin-4-one; 3,5-bis(2-chlorobenzylidene)piperidin-4-one; 3,5-bis(2-bromobenzylidene)piperidin-4- Ketone; 3,5-bis(3,4-difluorobenzylidene)piperidin-4-one; 3,5-bis(3-fluorobenzylidene)piperidin-4-one; 3,5 - Bis(3,4-dihydroxybenzylidene)piperidin-4-one; 3,5-bis(3,4-dihydroxybenzylidene)-1-methylpiperidin-4-one; 3,5-bis(3,4-dihydroxybenzylidene)-tetrahydropyran-4-one; 3,5-bis(3,4-dihydroxybenzylidene)-tetrahydrothiopyran- 4-keto; 3,5-bis(3,4-difluorobenzylidene)-tetrahydropyran-4-one; 3,5-bis(bis(2-chloroethyl)aminobenzylidene )-tetrahydrothiopyran-4-one.

The present disclosure provides a method of generating mature mesenchymal stem cells (MSC) from lateral plate mesoderm comprising culturing the lateral plate mesoderm cells on an extracellular matrix in a MSC cell culture media comprising (i) fibroblast growth factor; (ii) platelet-derived growth factor (PDGF); (iii) epidermal growth factor (EGF) and (iv) ascorbic acid. Also claimed are MSCs obtained by said culture method and a method of treating cartilage and bone disease in a patient using said cells. In addition, a culture medium for deriving primitive streak mesendoderm cells from pluripotent stem cells comprising (a) activin; (b) WNT-signalling activator; and / or (c) fibroblast growth factor and a culture medium for deriving lateral plate mesoderm cells from primitive streak mesendoderm cells comprising (1) fibroblast growth factor; (2) bone morphogenetic protein; (3) follistatin; and optionally Rho-associated protein kinase (ROCK) inhibitor are claimed.