Lovastatin Hydroxy Acid (sodium salt) is a highly potent and competitive inhibitor of HMG-CoA reductase (HMGCR) with a Ki value of 0.6nM[1]. By inhibiting HMGCR, Lovastatin Hydroxy Acid (sodium salt) blocks the mevalonate pathway, thereby regulating intracellular cholesterol homeostasis and downstream lipid metabolism processes[2]. Lovastatin Hydroxy Acid (sodium salt) is commonly used in research related to lipid metabolism signaling pathways, hypercholesterolemia, atherosclerosis, and associated cardiovascular diseases[3,4].
In vitro, when co-incubated with human liver microsomes and paclitaxel at 37℃ for 20min, Lovastatin Hydroxy Acid (sodium salt) (10, 100μM) concentration-dependently inhibited CYP2C8-mediated 6α-hydroxylation of paclitaxel, with an inhibition constant (Ki) of 48.9μM and an IC50 value of 54.9μM[5]. Treatment of hippocampal slices from Fmr1 knockout mice with Lovastatin Hydroxy Acid (sodium salt) (50μM) for 30min effectively corrected the excessive protein synthesis, restoring it to levels comparable to wild-type (WT) slices, and significantly reduced the levels of phosphorylated ERK1/2[6].
In vivo, administration of Lovastatin Hydroxy Acid (sodium salt) (10mg/kg/day; once daily; s.c.), starting 3 days before training and continuing throughout the training period, to nf1+/- mice reversed the spatial learning deficits observed on day 7 in the probe trial of the Morris water maze, restoring the exploration time in the target quadrant to a level indistinguishable from that of wild-type mice[7]. Pretreatment of Fmr1 knockout mice with Lovastatin Hydroxy Acid (sodium salt) (100mg/kg) via intraperitoneal injection 1h prior significantly reduced the incidence and severity scores of audiogenic seizures (AGS), and prolonged the latency to seizure onset[6].
References:
[1] ALBERTS A W. Lovastatin and simvastatin-inhibitors of HMG CoA reductase and cholesterol biosynthesis[J]. Cardiology, 1990, 77(Suppl 4): 14-21.
[2] CLENDENING J W, PANDYRA A, BOUTROS P C, et al. Dysregulation of the mevalonate pathway promotes transformation[J]. Proceedings of the National Academy of Sciences, 2010, 107(34): 15051-15056.
[3] KRUKEMYER J J, TALBERT R L. Lovastatin: a new cholesterol-lowering agent[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 1987, 7(6): 198-209.
[4] FURBERG C D, ADAMS H P Jr, APPLEGATE W B, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group[J]. Circulation, 1994, 90(4): 1679-1687.
[5] TORNIO A, PASANEN M K, LAITILA J, et al. Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8[J]. Basic & clinical pharmacology & toxicology, 2005, 97(2): 104-108.
[6] MUSCAS M, LOUROS S R, OSTERWEIL E K. Lovastatin, not simvastatin, corrects core phenotypes in the fragile X mouse model[J]. eneuro, 2019, 6(3).
[7] LI W, CUI Y, KUSHNER S A, et al. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1[J]. Current Biology, 2005, 15(21): 1961-1967.
Lovastatin Hydroxy Acid (sodium salt)是一种高效的竞争性HMG-CoA还原酶（HMGCR）抑制剂，Ki值为0.6nM[1]。Lovastatin Hydroxy Acid (sodium salt)通过抑制HMGCR阻断甲羟戊酸途径，从而调节细胞内胆固醇稳态及下游脂类代谢过程[2]。Lovastatin Hydroxy Acid (sodium salt)通常用于脂质代谢相关信号通路、高胆固醇血症、动脉粥样硬化及相关心血管疾病的研究[3,4]。
在体外，Lovastatin Hydroxy Acid (sodium salt)（10, 100μM）与人肝微粒体及紫杉醇在37℃共同孵育20min，可浓度依赖地抑制CYP2C8介导紫杉醇6α-羟基化反应，抑制常数Ki为48.9μM，IC50值为54.9μM[5]。Lovastatin Hydroxy Acid (sodium salt)（50μM）处理Fmr1敲除小鼠海马体切片30min，有效纠正了海马体过度的蛋白质合成，使其恢复到与野生型（WT）切片相当的水平，并显著降低了磷酸化ERK1/2的水平[6]。
在体内，Lovastatin Hydroxy Acid (sodium salt)（10mg/kg/day; once daily; s.c.）于训练前3天开始并持续至训练期间）处理nf1+/-小鼠，可逆转其第7天在Morris水迷宫探测试验中表现出的空间学习缺陷，使其在目标象限的探索时间恢复至与野生型小鼠无差异的水平[7]。Lovastatin Hydroxy Acid (sodium salt)（100mg/kg）通过腹腔注射预处理Fmr1敲除小鼠1h，显著降低了小鼠听源性癫痫（AGS）的发生率和严重程度评分，并延长了癫痫发作的潜伏期[6]。