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.
|Number of pages||1|
|Issue number||Issue 1 Supplement|
|Publication status||Published - Sep 2013|
- type 2 diabetes
- animal experiments
Patterson, S., de Kort, M., Dokter, W. H. A., Bos, E. S., Miltenburg, A. M. M., & Flatt, P. R. (2013). Pharmacological characterisation of a novel long-acting CarboCarrier® D-Ala8GLP-1 for treatment of Type 2 diabetes. Diabetologia, 56(Issue 1 Supplement), S351. .