For research use only. Not for therapeutic Use.
BMS-820132 is an orally active and partial glucokinase (GK) activator with a AC50 of 29 nM. BMS-820132 decreases the glucose levels in glucose tolerance test (OGTT) model in normal rats, but not Zucker diabetic fatty (ZDF) rats. BMS-820132 exhibits pharmacological toxicity secondary to strong GK activation[1][2].
BMS-820132 (compound 31) (3 μmol/kg, 30 μmol/kg; po; single dose) decreases glucose levels in high-fat diet-induced obese (DIO) mice, in an oral glucose tolerance test (OGTT)[1].
BMS-820132 (10-200 mg/kg; po; once daily for 1 mo) results in body weight reduction in normal rat but not ZDF rats, indicating that the toxicity is secondary to the exaggerated pharmacology of potent GK activation[2].
BMS-820132 (10 mg/kg, 60 mg/kg, 120 mg/kg; po; once daily for 1 mo) results insignificant effects on dogs food consumption[2].
Pharmacokinetic Analysis in Animal Model[1]
Route
Dose (mg/kg)
Cmax (μM)
Tmax (h)
AUC0-24 h (μM·h)
T1/2 (h)
CLTp (mL/min/kg)
Vss (L/kg)
F (L/kg)
mouse
iv
2.5
24.9
2.1
2.9
0.3
po
5
14.1
0.5
49.7
100
rat
iv
2.5
16.6
0.9
4.4
0.3
po
5
13.0
0.9
29.5
90
dog
iv
3
12.3
1.8
7.2
0.5
po
3
4.9
0.8
8.0
66
monkey
iv
3
3.8
1.9
22.7
1.1
po
3
3.8
1.3
0.57
15
| Catalog Number | I044056 |
| CAS Number | 1001419-18-6 |
| Synonyms | 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-N-[1-(diethoxyphosphorylmethyl)pyrazol-3-yl]-5-propan-2-yloxybenzamide |
| Molecular Formula | C26H33N6O7P |
| Purity | ≥95% |
| InChI | InChI=1S/C26H33N6O7P/c1-5-36-40(35,37-6-2)17-32-11-8-23(30-32)29-25(33)19-12-20(38-18(3)4)14-21(13-19)39-24-16-27-22(15-28-24)26(34)31-9-7-10-31/h8,11-16,18H,5-7,9-10,17H2,1-4H3,(H,29,30,33) |
| InChIKey | OYUDYQMFVRHPIY-UHFFFAOYSA-N |
| SMILES | CCOP(=O)(CN1C=CC(=N1)NC(=O)C2=CC(=CC(=C2)OC(C)C)OC3=NC=C(N=C3)C(=O)N4CCC4)OCC |
| Reference | [1]. Shi Y, et al. Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1H-pyrazol-1-yl)methyl)phosphonate (BMS-820132). J Med Chem. 2022;65(5):4291-4317. |
