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Growth hormone secretagogue receptor based protein, nucleic acids and methods and uses thereof

A technology for secretagogues and growth hormones, applied in the field of compounds

Active Publication Date: 2016-01-13
KUNMING INNOGEN PHARM TECH CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in vitro studies have shown that UAG (Kojima, Hosoda et al.1999) and obestatin (Zhang, Renetal.2005) cannot bind to GHS-R1a

Method used

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  • Growth hormone secretagogue receptor based protein, nucleic acids and methods and uses thereof
  • Growth hormone secretagogue receptor based protein, nucleic acids and methods and uses thereof
  • Growth hormone secretagogue receptor based protein, nucleic acids and methods and uses thereof

Examples

Experimental program
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Effect test

Embodiment

[0101] Attenuation of circulating ghrelin may reduce calorie intake and promote fat energy utilization. In this way, a mammalian expression plasmid encoding the ligand-binding region of GHS-R1a, particularly the N-terminal (Nt) and / or extracellular loops 1 and 2 (EC1, EC2) was constructed and linked to the murine IgG constant region (Fc) Fusion, composed of GHSR / Fc( figure 1 A). These fusion proteins were successfully expressed in vivo by intramuscular injection followed by electrotransfer in mouse gastrocnemius muscle tissue. The fusion molecule omits the sequence corresponding to the transmembrane domain of the receptor, so that the product of GHSR / Fc can be secreted extracellularly.

[0102] result

[0103] Effectiveness of the GHSR molecule

[0104] First, through the transient expression of the plasmid vector ( figure 1 A) Confirm the expression and secretion of the fusion protein in rat skeletal muscle cell L6 under in vitro conditions. 48 hours after transfection,...

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Abstract

Ghrelin is a peptide hormone that binds its receptor, growth hormone secretatgogue receptor la (GHS-Rl a, ghrelin receptor), to promote adiposity and obesity in mammals. Ghrelin and its receptor are targets for therapeutic intervention to treat obesity-related disease and cancer. A soluble decoy GHS-R1 a receptor is developed that binds ghrelin in the periphery, preventing ghrelin from binding GHS-R1 on cells, thereby antagonizing ghrelin to treat obesity-related pathological conditions and cancer. GHS-R1 a is a transmembrane protein comprising an N-terminal extracellular domain (Nt), seven transmembrane regions and three extracellular loops (EC1, EC2 and EC3). The Nt, EC1 and EC2 are linked together, in the absence of the transmembrane regions, and fused to a Fc from an immunoglobulin, to create the decoy GHS-R1 a fusion protein, GHSR-Fc. The GHSR-Fc inhibits adiposity and weight gain in mice on a high fat diet (HFD), while the Nt and ECs on their own have no significant effect.

Description

[0001] This application claims the benefit of U.S.C. § 119 of the PCT International Application based on U.S. Provisional Patent Application No. 61 / 748,267, filed March 14, 2013, the entire contents of which are hereby incorporated by reference. technical field [0002] The present invention relates to a compound and its application for curbing excessive weight gain, preventing and treating obesity and related diseases. Background technique [0003] Excessive obesity is a risk factor contributing to many chronic diseases including type II diabetes, cardiovascular disease and cancer (Wang & MecPherson 2011). Research results show that moderate weight loss has a positive effect on reducing cardiovascular risk factors (Blackburn1995, Pi-Suneyer1996) and also reduces the risk of type II diabetes and diabetic complications (Bosello, Armellinietal1997). [0004] Lifestyle intervention is the currently recommended first-line approach to weight control, with the goal of reducing cal...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K47/48A61P3/04A61P3/08C07K14/72
CPCC07K14/72C07K2319/30A61P1/00A61P1/18A61P15/00A61P3/04A61P35/00A61P3/06A61P3/08A61P9/00A61P9/12A61P3/10A61K48/00C07K14/723C07K2319/32
Inventor 王庆华尤尼思·安尼尼
Owner KUNMING INNOGEN PHARM TECH CO LTD
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