VULM 1457

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]. IC50 & Target: acyl-CoA^[1] 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 B_maxHypox being 127±10 and K_D 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].