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ADP Glucose Receptor as a Target for Disorders Involving Platelet Aggregation

Technology Application

A screen for P2Y12 using ADP-glucose has been developed. This assay monitors the P2Y12 receptor reactivity in a high-throughput format and thus will lead to the identification of antagonists and/or agonists that are specific to the P2Y12 receptor. Antagonists will mainly target platelet aggregation. Agonists and antagonists might also be used in the treatment of gastrointestinal disorders (e.g. inflammatory bowel disease) that require modulation of smooth muscle contractility. P2Y12 receptor signaling also induces vasorelaxation. Antagonists and agonists can be used to modulate vascular smooth muscle function by acting as vasoconstrictors or vasodilators with applications to cardiovascular disorders. A diagnostic may also be developed using the antibodies to assay for normal ADP-glucose cell function. Other areas involving smooth muscle contractility dysfunction that may benefit from ADP-glucose receptor signaling include allergic, inflammatory, respiratory, infectious, autoimmune, psychiatric, and metabolic disorders.

Detailed Technology Description

University of California, Irvine researchers have discovered that the P1Y12 receptor can be activated by a specific natural ligand, ADP-glucose, and that upon activation the receptor transduces a G-protein coupled intracellular signal. Researchers have also identified this receptor's immunogenic peptides. These immunogenic peptides can be used to induce antibodies to the receptor and they can be used in assays to isolate ADP-glucose receptor ligands, agonists, or antagonists. Researchers have also found that signaling through the ADP-glucose receptor leads to potent effects on smooth muscle contractile responses.

Supplementary Information

Patent Number: US6790608B2
Application Number: US2001780576A
Inventor: Civelli, Olivier | Nothacker, Hans Peter | Wang, Zhiwei | Reinscheid, Rainer
Priority Date: 20 Sep 2000
Priority Number: US6790608B2
Application Date: 9 Feb 2001
Publication Date: 14 Sep 2004
IPC Current: G01N003366
US Class: 435004 | 4350071 | 530350
Assignee Applicant: The Regents of the University of California
Title: Methods of identifying an ADP-glucose receptor ligand, agonist or antagonist | Methods of identifying and ADP-glucose receptor ligand, agonist or antagonist
Usefulness: Methods of identifying an ADP-glucose receptor ligand, agonist or antagonist | Methods of identifying and ADP-glucose receptor ligand, agonist or antagonist
Summary: ADP-G or (A) is useful for treating an ADP-G receptor associated condition e.g. cardiovascular function disorder, where the therapeutic composition induces vasorelaxation. The new method is useful in identifying agonists or antagonists and a ligand of (I) (claimed). Agonists or antagonists of (I) are useful therapeutically for preventing or ameliorating conditions associated with (I) such as cardiovascular disorders (e.g. ischemia, hypertension, hypotension, anginal pectoris, myocardial infarction, stroke, congestive heart failure, shock, erectile dysfunction, orthostatic intolerance and migraine), gastrointestinal disorders (e.g. diarrhea, gastritis, inflammatory bowel disease), immune disorders (e.g. immunodeficiency disorders, autoimmune disorders, rheumatoid arthritis), infections caused by bacteria, fungi, protozoa or virus, respiratory disorders (e.g. asthma, pneumonia, bronchitis), kidney disorders (e.g. glomerulonephritis, renal failure, lupus), hepatobiliary disorders (e.g. jaundice, cirrhosis, hepatitis), endocrine disorders (e.g. pituitary, thyroid or adrenal dysfunctions), musculoskeletal disorders (e.g. osteoporosis, muscular dystrophies), nervous system disorders (e.g. Parkinson's and Alzheimer's disease), psychotic disorders (e.g. depression, anxiety, schizophrenia), cancer, pain, glycogen storage diseases and disorders of body weight. A ligand of (I) is useful therapeutically, in detecting normal or abnormal expression of (I) in an isolated sample or in in vivo diagnostic imaging procedures, and targeting specifically a diagnostic group to cells and tissues that express (I).
Novelty: Identifying an agonist, antagonist or ligand of an ADP-glucose receptor, for treating cardiovascular, gastrointestinal, kidney, endocrine, immune disorders, and bacterial, viral, protozoal or fungal infections

Industry

Disease Diagnostic/Treatment

Sub Category

Cancer/Tumor

Application No.

6790608

Others

Tech ID/UC Case

18906/2001-001-0

Related Cases

2001-001-0

*Abstract

Recently, activation of the P2Y12 G-protein coupled receptor (GPCRs) has been shown to be central to platelet aggregation. Drugs preventing platelet aggregation are being tested, but one that would be specific to the P2Y12 receptor would capture a large market share. Developing drugs for the P1Y12 receptor is difficult, because it is a receptor that is naturally activated by ADP. Since practically every cell expresses ADP-activatable receptors, developing a drug screening program directed specifically at the P2Y12 receptor has not been possible.

*IP Issue Date

Sep 14, 2004

*Principal Investigator

Name: Olivier Civelli

Department:

Name: Hans-Peter Nothacker

Department:

Name: Rainer Reinscheid

Department:

Name: Zhiwei Wang

Department:

Country/Region

USA