Identification and use of growth hormone secretagogue receptor type 1A antagonists

a technology of growth hormone secretagogue and receptor type, applied in the direction of biological testing, biological material analysis, dipeptide ingredients, etc., can solve the problems of reduced mobility, decreased quality of life, and no convincing treatment currently available for reducing body weight effectively and acceptably

Inactive Publication Date: 2006-02-23
NOVO NORDISK AS
View PDF5 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It also causes considerable problems through reduced mobility and decreased quality of life.
Except for exercise, diet and food restriction, no convincing treatment for reducing body weight effectively and acceptably currently exist.
Even mild obesity increases the risk of premature death, diabetes, hypertension, atherosclerosis, ...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Identification and use of growth hormone secretagogue receptor type 1A antagonists

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0061] Identification of Ligands for the Receptor GHS-R 1A

[0062] Transfection

[0063] Lipofectamine (Life Technologies, Rockville, Md., U.S.A.) was used for transfection of BHK cells with a GHS-R 1A expression vector (Howard, A. D. et al. (1996), Science 273, 974-977).

[0064] Receptor Binding Assay

[0065] Receptor binding was assayed as described in Hansen, B. S. et al (1999) Eur. J. Endocrinol. 141:180-189. Briefly, crude membranes from stably transfected BHK / GHS-R 1A cells were suspended at 0.5 mg protein / ml in homogenization buffer (25 mM Tris-base, 2.5 mM EDTA, 10 mM MgCl2 and 30 μg / ml bacitracin). In a microtiter plate 10 μl membrane suspension was combined with either 35S-labelled MK0677 (see Example 4) (Amersham Pharmacia Biotech, Essex, UK) or 2-3H-adenosine (Amersham) as well as binding buffer (2.5 mM Tris-base, 2.5 mM EDTA and 10 mM MgCl2) to a total volume of 250 μl. Non-specific binding was determined by adding 10 μM MK0677 (see Example 4) or 10 μM adenosine to the assay...

example 2

[0071] Identification of Adenosine as a Ligand for the Receptor GHS-R 1A

[0072] The methods of example 1 were used. Adenosine was found to be a potent ligand for the GHS-R 1A (EC50˜50 nM using the Ca++ assay described above). Binding studies were performed to characterize the binding of adenosine to the GHS-R 1A, and a KD of 87±10 nM was determined.

[0073] Adenosine was, however, unable to stimulate GH secretion from rat pituitary cells (assay described e.g. in Hansen, B. S. et al (1999) Eur. J. Endocrinol. 141:180-189).

example 3

[0074] Adenosine Does Not Stimulate Growth Hormone Release, but Stimulates Feeding

[0075] The effect on GH release was studied in Halothane anaesthetized male Wistar rats after intracerebroventricular (icv) and intravenous (iv) administration of adenosine and also in pentobarbital anaesthetized catheterized female Sprague Dawley (SD) rats after iv administration. Vehicle or adenosine was given to groups of rats (n=4-6) in the following doses: 10 μg / rat and 100 μg / rat icv dissolved in 5 μ; saline, 1 mg / kg iv and also 10 mg / kg iv to the SD rats. Blood samples were obtained from anaesthetized animals before dosing, and either 10 min after dosing or by frequent blood sampling through a catheter up until 45 min after dosing. The plasma was analyzed for rat GH.

[0076] The effect on feeding was studied in conscious non-deprived male Wistar rats (n=7-10) after icv dosing of vehicle or adenosine (1 μg / rat and 10 μg / rat in 5 μl saline). Food intake was measured in feeding boxes with standard ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Currentaaaaaaaaaa
Login to view more

Abstract

Compounds that are ligands for the growth hormone secretagogue receptor type 1A (GHS-R 1A), as well as pharmaceutically acceptable salts of such compounds, are useful for the manufacture of medicaments for the regulation of food intake.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS [0001] This patent application is a continuation of copending U.S. patent application Ser. No. 10 / 649,386, filed Aug. 27, 2003, which is a continuation of U.S. patent application Ser. No. 09 / 771,770, filed Jan. 29, 2001, and claims the benefit of U.S. Provisional Patent Application 60 / 181,303, filed Feb. 9, 2000, and Danish Patent Applications PA 2000 00161 and PA 2000 01107 filed Feb. 1, 2000 and Jul. 17, 2000, respectively, the entire of content of each of which is hereby incorporated by reference.FIELD OF THE INVENTION [0002] This invention relates to the use of a compound that is a ligand for the growth hormone secretagogue receptor type 1A (GHS-R 1A) for the regulation of food intake or food intake. The present invention also embraces pharmaceutical compositions comprising these compounds and methods of using the compounds and their pharmaceutical compositions. BACKGROUND OF THE INVENTION [0003] Stimulation of food intake is import...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K49/00A61K31/00A61K31/454A61K31/4747A61K31/7076A61K38/05A61K38/17A61K38/25G01N33/74
CPCA61K31/00A61K31/44A61K31/454A61K31/4747A61K31/7076G01N2500/00A61K38/06A61K38/17A61K38/25A61K49/0008G01N33/74A61K38/05
Inventor ANDERSEN, MAIBRITTHANSEN, BIRGITRAUN, KIRSTENTULLIN, SORENTHIM, LARS
Owner NOVO NORDISK AS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap