| Description |
VULM 1457 is a potent inhibitor of cholesterol acyltransferase (acyl-CoA). VULM1457 significantly reduces production and secretion of adrenomedullin (AM) and down-regulates AM receptors on human hepatoblastic cells. VULM 1457 has remarkable hypolipidaemic activity and improves the overall myocardial ischaemia-reperfusion injury outcomes. VULM 1457 has the potential for the research of diabetes mellitus and hypercholesterolaemia[1][2].
|
| Related Catalog |
|
| Target |
ACAT
|
| In Vitro |
VULM1457 (0.03 and 0.1 µM) significantly down-regulates specific AM receptors on HepG2 cells, reduced AM secretion of HepG2 cells exposed to hypoxia[1].VULM1457 negatively regulates cell proliferation induced by AM[1]. Preincubation of HepG2 cells with VULM1457 (0.1 µM) significantly reduces the total number of specific [125I]AM binding identified on cells at untouched affinity. Preincubation of HepG2 cells with high concentrations of VULM1457 (1.0 and 10.0 µM) significantly modifies the characteristics of binding of AM, i.e[1]. Preincubation of HepG2 cells with VULM1457 (0.1 µM) significantly reduces the specific [125I]AM binding on hypoxic cells with BmaxHypox being 127±10 and KD 0.06±0.11 nM. Preincubation of cells with VULM1457 (0.1 µM) significantly enhances the number of cells (24.2±6 %) and higher concentrations of VULM1457 (1.0 and 10.0 µM) reduces the total number of cells. With the high concentrations of VULM1457 (1.0 and 10.0 µM), the reductions in [125I]AM specific binding on HepG2 cells is markedly attenuated[1].
|
| In Vivo |
VULM 1457 significantly reduces atherogenic activity in animal experimental atherosclerosis[1]. VULM 1457 protect the hearts of diabetic–hypercholesterolaemic rats against ischaemia/reperfusion injury in vivo[2]. VULM 1457 (50 mg/kg/day; administered as an admixture to the fat-cholesterol diet for 5 days) significantly decreases plasma total cholesterol levels (1.7±0.1 mM vs. 2.9±0.5 mM in diabetic–hypercholesterolaemic animals). The hypolipidaemic effect of VULM 1457 is also observed in the liver of DM-HCH rats (3.9±0.2 mg/g vs. 7.4±1.0 mg/g)[2]. Animal Model: Male Wistar rats (250-300 g body weight), fed a standard diet and tap water ad libitum[2] Dosage: 50 mg/kg/day Administration: Administered as an admixture to the fat-cholesterol diet for 5 days Result: Improved the overall myocardial ischaemia-reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis, aside from remarkable hypolipidaemic activity.
|
| References |
[1]. J Drímal, et al. The ACAT inhibitor VULM1457 significantly reduced production and secretion of adrenomedullin (AM) and down-regulated AM receptors on human hepatoblastic cells. Gen Physiol Biophys. 2005 Dec;24(4):397-409. [2]. Adameová A, et al. The myocardial infarct size-limiting and antiarrhythmic effects of acyl-CoA:cholesterol acyltransferase inhibitor VULM 1457 protect the hearts of diabetic-hypercholesterolaemic rats against ischaemia/reperfusion injury both in vitro and in vivo. Eur J Pharmacol. 2007;576(1-3):114-121.
|
