VULM 1457 是一种有效的胆固醇酰基转移酶 (acyl-CoA) 抑制剂。VULM1457 显着降低肾上腺髓质素 (AM) 的产生和分泌,并下调人肝母细胞上的 AM 受体。VULM 1457 具有显着的降血脂活性,并改善了整体心肌缺血再灌注损伤结果。VULM 1457 具有研究糖尿病和高胆固醇血症的潜力。
生物活性 | VULM 1457 is a potent inhibitor of cholesterolacyltransferase(acyl-CoA). VULM1457 significantly reduces production and secretion ofadrenomedullin(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[1] | |
体外研究 (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 BmaxHypoxbeing 127±10 and KD0.06±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].
|
体内研究 (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 waterad 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. |
|
分子量 | |
性状 | |
Formula | |
CAS 号 | |
运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
溶解性数据 | In Vitro: DMSO : 250 mg/mL(556.09 mM;Need ultrasonic) 配制储备液 1 mM | 2.2243 mL | 11.1217 mL | 22.2435 mL | 5 mM | 0.4449 mL | 2.2243 mL | 4.4487 mL | 10 mM | 0.2224 mL | 1.1122 mL | 2.2243 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 |