| Description: |
Ingliforib is a glycogen phosphorylase inhibitor, with IC50s of 52, 352 and 150 nM for liver, muscle and brain glycogen phosphorylase, and has cardioprotective activity. |
| Target: |
IC50: 52 nM (liver Glycogen phosphorylase), 352 nM (Muscle Glycogen phosphorylase), 150 nM (Barin Glycogen phosphorylase)[1] |
| In Vivo: |
Ingliforib (15 mg/kg) potently reduces infarct size by 52%, and decreases plasma glucose and lactate concentrations in openchest anesthetized rabbits. Ingliforib (15 mg/kg) also inhibits myocardial glycogen phosphorylase a (GPa) and total glycogen phosphorylase (GP) activity in anesthetized rabbits[1]. |
| In Vitro: |
Ingliforib is a glycogen phosphorylase inhibitor, and inhibits the myocardial GP isoforms (muscle and brain) with IC50s of 352 and 150 nM, respectively, also a potent inhibitor of the liver isoform (IC50 of 52 nM). Ingliforib (0.1, 1, 10 μM) dose-dependently reduces infarct size in the isolated rabbit hearts[1]. |
| Animal Administration: |
Rabbits[1] Male New Zealand White rabbits (3 to 4 kg) are used in the assay. At least 1 h after surgery, when arterial pressure, heart rate (HR), and rate-pressure product (RPP) have stabilized for at least 30 min (baseline), the rabbits receive a bolus of either 15.4 mg/kg of Ingliforib or vehicle (administered in 15 s), followed by a constant infusion of 23.1 mg/kg/h Ingliforib or vehicle at the same dose volume for a total of 3.5 h. Sixty minutes after starting the infusion, regional ischemia is produced by tightening the coronary artery snare for 30 min. The snare is released, and the heart is reperfused for an additional 120 min. Myocardial ischemia is confirmed by regional cyanosis and ST segment elevation; reperfusion is confirmed by reactive hyperemia and rapid decline of the ST elevation. At the end of either the ischemic period or reperfusion period, each rabbit is euthanized with an intravenous overdose of pentobarbital sodium (100 mg/kg). The heart is quickly excised and prepared for measurement of glycogen phosphorylase activity and glycogen content, or mounted and perfused with physiological saline at 38.5°C for subsequent determination of infarct size[1]. |
| References: |
[1]. Tracey WR, et al. Cardioprotective effects of ingliforib, a novel glycogen phosphorylase inhibitor. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1177-84. |
