Merck + Co., Inc.

Margaret A Cascieri

Douglas J MacNeil

Catherine D Strader

Carina P Tan

Lin-Lin Shiao

Roy G Smith

David L Linemeyer

David H Weinberg

Kathleen A Sullivan

Leonardus H T Van Der Ploeg

Kevin R Lynch

Andrew D Howard

Marvin L Bayne

Michael P Graziano

Michael R Tota

John G Menke

Diana Benincasa

Euan MacIntyre

Patricia J Hey

Gary A Chicchi

Lyndon J Mitnaul

Joy D Applebaum

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.

Cell fusion assays using fluorescence resonance energy transfer

A new galanin receptor, GALR3, is described. Also provided are nucleic acids encoding same and various assays to identify ligands particular to said receptor. Ligands so identified are useful for the treatment of obesity, treatment of pain, and treatment of cognitive disorders.

Nucleotide encoding human galanin receptor 3 (GALR3)

Modified human neuropeptide Y1 Receptors

Neuropeptide Y receptor

The combination of a metabolic rate modifying agent (e.g., a .beta..sub.3 adrenergic receptor agonist) and a feeding behavior modifying agent (e.g., a NPY5 antagonist) is useful in the treatment of obesity and diabetes, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients. Methods of treating obesity and diabetes are also described.

Combination therapy for the treatment of diabetes and obesity

A synthetic human glucagon (hGlu) binding protein designated hGlu.DELTA.252-259 binding protein is cloned, expressed and used in an in vitro assay to screen for compounds that bind to the synthetic binding protein, including compounds that specifically stimulate or inhibit the binding of glucagon to the synthetic receptor. The invention includes the assay, the synthetic binding protein used in the assay, DNA encoding the synthetic binding protein, cells expressing the synthetic binding protein, and compounds identified through the use of the synthetic binding protein.

Synthetic glucagon binding proteins

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.

A synthetic gene encoding a 71-amino acid analog of human insulin-like grouwth factor (hIGF-I) has been constructed and expressed in the yeast, Saccharomyces cerevisiae. The protein analog, IGF132, contains the first 17 amino acids of the B chain of human insulin in place of the first 16 amino acids of hIGF-I. The purified hybrid protein has high affinity for the type I IGF recepto (12 nM) yet has drastically reduced affinity for human serum carrier proteins (&gt;1000 nM). This analog is 5 to 10 times more active than normal hIGF-I in stimulating DNA synthesis in 3T3 cells and is a more active growth factor in vivo due to its reduced affinity for serum carrier proteins. Other proteins with similar properties have also been constructed. The protein analogs thus have a variety of utilities such as in promoting lactation in animals; promoting growth and feed efficiency in animals; improving carcass quality by increasing lean and decreasing fat; promoting wound healing in animals, including humans; promoting glucose utilization in skeletal muscle, and stimulating erythropoiesis, the production of red blood cells.

Human insulin-like growth factor analoges with reduced binding to serum

Growing community of inventors

East Windsor, NJ, United States of America

Margaret A Cascieri