Category
Glucagon
ID
NNC9204-0043
Amount per vial
1000 nmol
Glucagon is s a 29 amino acid residue peptide hormone produced by the alpha-cells in the pancreas. Together with insulin it regulates blood glucose levels. It stimulates release of glucose from the liver at low blood glucose levels by increasing gluconeogenesis and glycogenolysis, and by suppressing glycolysis. Glucagon is used to treat insulin-induced severe hypoglycemia.
NNC9204-0043 is a long-acting glucagon analogue.
Category
Glucagon
ID
NNC9204-0043
Amount per vial
1000 nmol
Property | NNC9204-0043 | Native glucagon |
MW (Da) | 4138.6 | 3482.7 |
pI (calculated) | 4.9 | 6.4 |
Sequence substitutions (compared to reference) | 17K, 18K, 21E, 24K(2xOEG-gGlu-C18 diacid), 27L | - |
Extinction coefficient (calculated, 280 nm) | 8480 | 8480 |
Figure 1
2D sketch of the structure of NNC9204-0043. The compound has the following sequence substitutions compared to native glucagon: 17K, 18K, 21E, 24K(2xOEG-gGlu-C18 diacid), 27L.Figure 2
The sequence of native glucagon.The binding affinity to human GCGR was measured by the ability of the compounds to displace 125-iodine-labelled glucagon from baby hamster kidney (BHK) cell plasma membranes stably expressing the human GCGR in a scintillation proximity assay (SPA) setup. The in vitro potencies were determined by luciferase assays using BHK cells stably transfected with the human GCGR and CRE luciferase. Since albumin binding is a key mechanism for the design of NNC09204-0043, be aware that the apparent affinity and potency will be very dependent on whether the in vitro assays contain albumin or not.
Compound | Potency
No HSA (EC50, pM ± SEM) | Potency
1% HSA (EC50, pM ± SEM) |
Native glucagon | 9.8 ± 0.7 (n=194) | 8.4 ± 0.7 (n=94) |
NNC9204-0043 | 7.1 ± 0.6 (n=52) | 440 ± 57 (n=32) |
Receptor affinity
No BSA (IC50, nM ± SEM ) | Receptor affinity
0.2% BSA (IC50, nM ± SEM ) | |
Native glucagon | 0.63 ± 0.02
(n=142) | 0.33 ± 0.01 (n=138) |
NNC9204-0043 | 0.45 ± 0.04
(n=42) | 31 ± 2.7 (n=40) |
The terminal half-life of NNC9204-0043 is 5-6 h following s.c. administration of a single 3 nmol/kg dose in mice.