Pharmacological characterisation of a novel long-acting CarboCarrier® D-Ala8GLP-1 for treatment of Type 2 diabetes

Steven Patterson; Martin de Kort; Wim H. A. Dokter; Ebo S. Bos; Andre M. M. Miltenburg; Peter  R. Flatt

Pharmacological characterisation of a novel long-acting CarboCarrier® D-Ala8GLP-1 for treatment of Type 2 diabetes

Steven Patterson, Martin de Kort, Wim H. A. Dokter, Ebo S. Bos, Andre M. M. Miltenburg, Peter R. Flatt

Biological and Biomedical Sciences

Research output: Contribution to journal › Meeting abstract › peer-review

Abstract

Novel long-acting GLP-1 analogues were synthesized using CarboCarrier® technology. Pharmacological properties of Org 249305-1 in which an ATIII binding pentasaccharide, derived from Idraparinux, was conjugated to Lys37 of D-Ala8-GLP-1 amide are reported. Methods and Results: In vivo half-life of Org 249305-1 in rat and mouse was ~ 11h, with resistance to DPP-IV degradation. Insulin secretion from clonal BRIN-BD11 cells and mouse islets was increased 2.1 – 4.1- fold (P<0.01-0.001) by Org 249305-1 at 10-8M – 10-6M. Org 249305-1 had EC-50 values of 10-6.7M and 10-7.0M for GLP-1 receptor binding and cAMP generation, respectively.

Original language	English
Article number	882
Pages (from-to)	S351
Number of pages	1
Journal	Diabetologia
Volume	56
Issue number	Issue 1 Supplement
Publication status	Published - Sep 2013

Keywords

type 2 diabetes
treatment
CarboCarrier
animal experiments

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{cf87b74535fd4432bd9b6edb9b9c01e0,

title = "Pharmacological characterisation of a novel long-acting CarboCarrier{\textregistered} D-Ala8GLP-1 for treatment of Type 2 diabetes",

abstract = "Novel long-acting GLP-1 analogues were synthesized using CarboCarrier{\textregistered} technology. Pharmacological properties of Org 249305-1 in which an ATIII binding pentasaccharide, derived from Idraparinux, was conjugated to Lys37 of D-Ala8-GLP-1 amide are reported. Methods and Results: In vivo half-life of Org 249305-1 in rat and mouse was ~ 11h, with resistance to DPP-IV degradation. Insulin secretion from clonal BRIN-BD11 cells and mouse islets was increased 2.1 – 4.1- fold (P<0.01-0.001) by Org 249305-1 at 10-8M – 10-6M. Org 249305-1 had EC-50 values of 10-6.7M and 10-7.0M for GLP-1 receptor binding and cAMP generation, respectively.",

keywords = "type 2 diabetes, treatment, CarboCarrier, animal experiments",

author = "Steven Patterson and {de Kort}, Martin and Dokter, {Wim H. A.} and Bos, {Ebo S.} and Miltenburg, {Andre M. M.} and Flatt, {Peter R.}",

year = "2013",

month = sep,

language = "English",

volume = "56",

pages = "S351",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "Issue 1 Supplement",

}

TY - JOUR

T1 - Pharmacological characterisation of a novel long-acting CarboCarrier® D-Ala8GLP-1 for treatment of Type 2 diabetes

AU - Patterson, Steven

AU - de Kort, Martin

AU - Dokter, Wim H. A.

AU - Bos, Ebo S.

AU - Miltenburg, Andre M. M.

AU - Flatt, Peter R.

PY - 2013/9

Y1 - 2013/9

N2 - Novel long-acting GLP-1 analogues were synthesized using CarboCarrier® technology. Pharmacological properties of Org 249305-1 in which an ATIII binding pentasaccharide, derived from Idraparinux, was conjugated to Lys37 of D-Ala8-GLP-1 amide are reported. Methods and Results: In vivo half-life of Org 249305-1 in rat and mouse was ~ 11h, with resistance to DPP-IV degradation. Insulin secretion from clonal BRIN-BD11 cells and mouse islets was increased 2.1 – 4.1- fold (P<0.01-0.001) by Org 249305-1 at 10-8M – 10-6M. Org 249305-1 had EC-50 values of 10-6.7M and 10-7.0M for GLP-1 receptor binding and cAMP generation, respectively.

AB - Novel long-acting GLP-1 analogues were synthesized using CarboCarrier® technology. Pharmacological properties of Org 249305-1 in which an ATIII binding pentasaccharide, derived from Idraparinux, was conjugated to Lys37 of D-Ala8-GLP-1 amide are reported. Methods and Results: In vivo half-life of Org 249305-1 in rat and mouse was ~ 11h, with resistance to DPP-IV degradation. Insulin secretion from clonal BRIN-BD11 cells and mouse islets was increased 2.1 – 4.1- fold (P<0.01-0.001) by Org 249305-1 at 10-8M – 10-6M. Org 249305-1 had EC-50 values of 10-6.7M and 10-7.0M for GLP-1 receptor binding and cAMP generation, respectively.

KW - type 2 diabetes

KW - treatment

KW - CarboCarrier

KW - animal experiments

M3 - Meeting abstract

VL - 56

SP - S351

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - Issue 1 Supplement

M1 - 882

ER -

Pharmacological characterisation of a novel long-acting CarboCarrier® D-Ala8GLP-1 for treatment of Type 2 diabetes

Abstract

Keywords

UN SDGs

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