45 results about "Chemoattractant receptors" patented technology

The present invention relates to compounds that bind to chemokine receptors, and having the formula

wherein each A, X, Y, R¹, R² and R³ are substituents. The present invention also relates to methods of using such compounds, such as in treating HIV infection and inflammatory conditions such as rheumatoid arthritis. Furthermore, the present invention relates to methods to elevate progenitor and stem cell counts, as well as methods to elevate white blood cell counts, using such compounds.

The present invention provides polynucleotides that encode the chemokine receptors 88-2B or 88C and materials and methods for the recombinant production of these two chemokine receptors. Also provided are assays utilizing the polynucleotides which facilitate the identification of ligands and modulators of the chemokine receptors. Receptor fragments, ligands, modulators, and antibodies are useful in the detection and treatment of disease states associated with the chemokine receptors such as atherosclerosis, rheumatoid arthritis, tumor growth suppression, asthma, viral infection, AIDS, and other inflammatory conditions.

The present invention is directed to compounds of Formula I:

I which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

Cyclopentyl compounds of Formula (I) are modulators of chemokine receptor activity:

wherein D, G, R², R³ and R⁸ in Formula (I) are defined herein. The compounds, and pharmaceutically acceptable salts and individual diastereomers thereof, are useful in the treatment and prevention of HIV infection, in delaying the onset of AIDS, and in the treatment of AIDS. The compounds are also useful for treating other diseases and conditions mediated by chemokine receptors.

Disclosed herein are compounds represented by Structural Formula (I):

(I), wherein the variables are defined herein. Also disclosed is the use of such compounds for inhibiting the G-protein coupled receptor referred to as chemoattractant receptor-homologous molecule expressed on Th2 (“CRTH2”) for the treatment of inflammatory disorders.

The present invention relates to a pyrimidine derivative of the formula (I) and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The pyrimidine derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.

The invention belongs to the fields of molecular biology and immunology, and relates to chimeric chemokines receptors capable of making T cells tend to tumor locations. Specifically, the chimeric chemokines receptors are formed in a manner that a peptide fragment of a generated factor secreted by efficiently-combined tumor cells or tumor stromal cells is connected with a transmembrane region originated from a high-affinity receptor and a signal domain peptide fragment capable of making the T cells efficiently migrated through hinge structures. A membrane outer peptide fragment receives a corresponding factor signal and transfers the signal into cells, and a related path for promoting T cell chemotaxis is started through an intracellular region of the signal domain peptide fragment capable of promoting the migration of the T cells, so that the T cells modified by the chimeric chemokines receptors have a characteristic of migrating to the corresponding factor high concentration direction, and a normal tumor killing activity is not weaken, so as to ensure the tumor adoptive cell therapy effector T cells can efficiently reach the tumor nidus locations, and play a role in treatment.

The present invention provides methods and compositions to reduce immune tolerance at specific sites. In one aspect, the present invention comprises methods and compositions to reduce tumorigenicity. In an embodiment, the present invention reduces recruitment of tolerance-inducing antigen presenting cells (APCs) or their precursors to a tumor and/or tumor draining lymph node by decreasing binding of at least one tumor-associated ligand to a chemokine receptor present on the tolerance-inducing APCs or APC precursors. In an embodiment, the chemokine receptor is CCR6 and the tumor-associated ligand is mip-3α. In another aspect, the present invention comprises methods and compositions to reduce immune tolerance to a virus. In an embodiment, the virus is HIV. The present invention further provides for the development of CCR6 antibodies and antagonists as therapeutic agents to prevent or reduce immune tolerance.

The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

Methods of identifying inhibitors of the fusion of two types of cells, particularly when fusion is mediated by the interaction of a viral protein and such cellular proteins as CD4 and chemokine receptors, are disclosed. The methods are suitable for identifying substances that are useful for the treatment and prevention of viral diseases. Particularly preferred methods are useful for the identification of inhibitors of HIV-1 infection.

The invention features methods of treating allergic asthma by administering to a subject a chimeric polypeptide that comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one of (a)-(d): (a) a moiety that binds to a T cell surface polypeptide, (b) a moiety that binds to a dendritic cell surface polypeptide, (c) a moiety that binds to a cell toxin, and (d) a cell toxin.

The present invention relates to an imidazo[1,2-c]pyrimidinylacetic acid derivative and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The imidazo[1,2-c]pyrimidinylacetic acid derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.

A method for treating cancer comprising applying peripheral blood from a patient or subject to an apheresis column loaded with a solid support comprising one or more binding reagents capable of specifically binding to a chemokine receptor, optionally the chemokine receptor CCR7, CCR5, CCR6, CCR8, CXCR4, CXCR7, CCR4, CCR9, CCR10, CXCR3 or CXCR5 or to a Treg receptor immobilized directly or indirectly on the support thus removing one or more chemokine receptor, optionally CCR7, CCR5, CCR6, CCR8, CXCR4, CXCR7, CCR4, CCR9, CCR10, CXCR3 or CXCR5 or Treg receptor expressing cells from the peripheral blood of the patient or subject. Various companion diagnostic methods and useful binding reagents are also described.