Category
Glucagon
ID
NNC0025-0926
Amount per vial
20 mg
Glucagon is a 29 amino acid peptide hormone liberated in the alpha cells of the islets of Langerhans. Glucagon has in general been viewed as the counter regulatory hormone to insulin in peripheral tissues, predominantly to the liver. An important contributor to the development of hyperglycemia in type 2 diabetes is inappropriately high glucose production from the liver. The primary physiological effect of glucagon is to stimulate hepatic glucose production by increasing both gluconeogenesis and glycogenolysis.
NNC0025-0926 was developed as an oral bioavailable small molecule capable of antagonizing glucagon signaling and thereby shut down the contribution from glucagon to hyperglycemia in T2DM.
Category
Glucagon
ID
NNC0025-0926
Amount per vial
20 mg
Compound | NNC0025-0926 |
MW (Da) | 582.49 |
Sum formula | C30H29Cl2N3O5
|
Proton-NMR (DMSO-d6): d 1.50-1.80 (4H, m), 2.08-2.38 (4H, m), 3.36-3.65 (2H, m), 4.14-4.24 (1H, m), 4.96 (2H, m), 6.17 (1H, t), 7.14 (1H, t), 7.18 (2H, d), 7.35 (2H, d), 7.42 (2H, d), 7.63 (2H,d), 7.78 (2H, d), 8.48 (1H, t), 8.55 (1H, s).
Analytical chiral HPLC: Chiralcel OF 250x4.6 mm. Isocratic eluent; isopropanol:n-heptane:TFA: 80:20:0.1, Rt = 67.3 min. Purity > 99.5 % ee
Figure 1
2D sketch of NNC0025-0926. (R)-3-{4-[1-(4-Cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid.Receptor | Affinity of NNC0025-0926
(IC50, nM) |
Rat GCGR | 43 |
Rat GIPR | 501 |
Human GCGR | 3.9 |
Human GIPR | 359 |
To examine the effects in vivo, NNC0025-0926 was tested in a glucagon-challenged rat model. The compound dose-dependently inhibited the glucagon-stimulated rise in blood glucose (see figure 3 in the Kodra et al. 2008 reference listed in the reference section). The minimum effective i.v. dose for NNC0025-0926 was 3 mg/kg.
Parameter | NNC0025-0926 |
Species | Rat |
Oral bioavailability (%) | 32 |
Half-life after i.v. dose (min) | 53 |
CL (ml/min/kg) i.v. | 26 |
Vz (l/kg) i.v. | 0.91 |