Merck + Co., Inc.

University of Pennsylvania

Schering Corporation

Catherine D Strader

Tung M Fong

Douglas J MacNeil

Margaret A Cascieri

John W Hess

David L Linemeyer

Carina P Tan

David H Weinberg

Joseph A Borkowski

Ruey-Ruey C Huang

Lin-Lin Shiao

Kyriacos Costa Nicolaou

Ralph F Hirschmann

Paul A Sprengeler

Richard W Ransom

Howard Y Chen

Myrna E Trumbauer

Eric McFee Parker

Sherrie Pietranico

Joseph M Salvino

Mark Stephen Rudinski

T R Reisine

The present invention is a cloned human BK-2 bradykinin receptor cloned from a human lung fibroblast cell line. A cDNA clone, also part of the instant invention, encodes a novel 364 amino acid protein (the BK-2 receptor) that has the characteristics of a seven transmembrane domain G-protein coupled receptor. The invention is used to express a BK-2 bradykinin receptor in a host mammalian cell to screen for pharmaceutical antagonists or agonists which bind to or interact with the BK-2 bradykinin receptor protein.

Cloned and expressed human bradykinin BK-2 receptor

A recombinant human neurokinin-3 receptor (hereinafter identified as human NK3R) is disclosed which has been prepared by polymerase chain reaction techniques. Also disclosed is the complete sequence of human NK3R complementary DNA; expression systems, including a CHO (chinese hamster ovarian cell line) stable expression system; and an assay using the CHO expression system. Human NK3R can be used in an assay to identify and evaluate entities that bind to the neurokinin-3 receptor.

Method for measuring human neurokinin-3 receptor ligand binding

Human neurokinin-3 receptor

Modified human neuropeptide Y1 Receptors

The present invention provides mammalian chimeric NPY Y.sub.5 receptors, nucleic acids and vectors encoding the receptors, methods for making the receptors, fragments or fusion proteins thereof using recombinant DNA methodology or chemical synthesis, and methods for using the receptors in screening systems to identify compounds for the treatment of various diseases.

Chimeric mammalian NPY Y.sub.5 receptors

Neuropeptide Y receptor

A transgenic non-human animal with alterations in a bradykinin B2 receptor gene is prepared by introduction of a gene encoding an altered bradykinin B2 receptor into a host non-human animal.

Bradykinin B2 receptor modified transgenic non-human animals

A novel mammalian neuropeptide Y receptor and method of making the receptor are provided. The invention includes DNA encoding the receptor, the receptor, assays employing the receptor, cells expressing the receptor, antibodies which bind specifically to the receptor, RNA encoded by the DNA sequence or its complementary sequence, and single-stranded DNA with a sequence complementary to the RNA which encodes the receptor. The receptor and assays employing the receptor are useful for identifying compounds which bind to the receptor, including specific modulators of the receptor. Such compounds are useful for treating a variety of disease conditions, including obesity, diabetes, anxiety, hypertension, cocaine withdrawal, congestive heart failure, memory enhancement, cardiac and cerebral vasospasm, pheochromocytoma and ganglioneuroblastoma, and Huntington's, Alzheimer's and Parkinson's diseases.

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: ##STR1## wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, or R.sub.5 comprises a functional group which is chemically similar to that found in the peptide of interest.

Non-Peptide peptidomimetics

Recombinant human neurokinin-1 receptor (human NKIR) is disclosed which has been isolated by polymerase chain reaction techniques. Also disclosed is the complete sequence of human NKIR cDNA, expression systems containing said isolated cDNA, including a CHO (Chinese Hamster Ovarian Cell Line) stable expression systems, and an assay using the CHO eexpression system. NKIR, also known as substance P receptor, can be used in an assay to identify and evaluate entities that bind substance P receptor. The assay can also be used in conjunction with diagnosis and therapy to determine the body fluid concnetration of substance P in arthritis patients.

DNA encoding the human neurokinin-1 receptor

Recombinant human neurokinin-1 receptor (hereinafter identified as human NK1R) has been prepared by polymerase chain reaction techniques. The complete sequence of human NK1R complementary DNA has been identified. Expression systems, including a CHO (chinese hamster ovarian cell line) stable expression system; and an assay using the CHO expression system have been developed. NK1R, also known as substance P receptor, may be used in an assay to identify and evaluate entities that bind to the substance P receptor. The assay may also be used in conjunction with diagnosis and therapy to determine the body fluid concentration of substance P antagonists in arthritis patients.

Human neurokinin-1 receptor

A novel recombinant human neurokinin-1 receptor short form (hereinafter identified as human NK1R sF) is disclosed which has been prepared by polymerase chain reaction techniques. Also disclosed is the complete sequence of human NK1R sF complementary DNA; expression systems, including a CHO (Chinese hamster ovarian cell line) stable expression system; and an assay using the CHO expression system. NK1R sF, can be used in an assay to identify and evaluate entities that bind substance P receptor or NK1R sF. The assay can also be used in conjunction with diagnosis and therapy to determine the body fluid concentration of substance P antagonists in arthritis patients.

Method of using human neurokinin-1 receptor short form

Growing community of inventors

Verona, NJ, United States of America

Catherine D Strader