Lomitapide
(Synonyms: 洛美他派; AEGR-733; BMS-201038) 目录号 : GC16870
Lomitapide是一种微粒体甘油三酯转移蛋白（MTTP）抑制剂，IC50值为8nM。
Cas No.:182431-12-5
Sample solution is provided at 25 µL, 10mM.
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Lomitapide is an inhibitor of microsomal triglyceride transfer protein (MTTP), with an IC50 value of 8nM[1]. Lomitapide targets MTTP to block the assembly of apolipoprotein B (Apo B) lipoproteins in the liver and gut[2]. Lomitapide has been widely used as an anticancer agent to inhibit tumor growth and to develop novel combination therapies[3].
In vitro, Lomitapide significantly inhibited the proliferation of SW1990, AsPC-1 and BxPC-3 cells after 72 hours of treatment, with IC50 values of 5.689μM, 7.293μM and 6.962μM, respectively[4]. Treatment with 2.5μM Lomitapide for 48 hours significantly inhibited the viability of HCT116 cells, resulting in a decrease in intracellular ATP levels and an increase in ROS levels, and promoting autophagy in the cells[5]. Treatment with 2μM Lomitapide for 24 hours significantly reduced the permeability of the outer mitochondrial membrane in multiple myeloma (MM) cells and induced mitochondrial dysfunction[6].
In vivo, Lomitapide treatment via intraperitoneal injection at a dose of 20mg/kg (every other day for 10 days) significantly reduced HCT116 xenograft growth in mice without affecting body weight[7]. Oral administration of 0.5mg/kg of Lomitapide daily for 14 consecutive days can improve the neurological recovery of mice with middle cerebral artery occlusion (MCAO) and reduce the loss of neural tissue[8].
References:
[1] Sulsky R, Robl J A, Biller S A, et al. 5-Carboxamido-1, 3, 2-dioxaphosphorinanes, potent inhibitors of MTP[J]. Bioorganic & medicinal chemistry letters, 2004, 14(20): 5067-5070.
[2] Wu H T, Wu B X, Fang Z X, et al. Lomitapide repurposing for treatment of malignancies: A promising direction[J]. Heliyon, 2024, 10(12).
[3] Ivanova A, Wilson T M, Ghannad-Zadeh K, et al. Lomitapide enhances cytotoxic effects of temozolomide in chemotherapy-resistant glioblastoma[J]. JCI insight, 2025, 10(17): e186703.
[4] Wang Y, Zhang S, He H, et al. Repositioning Lomitapide to block ZDHHC5-dependant palmitoylation on SSTR5 leads to anti-proliferation effect in preclinical pancreatic cancer models[J]. Cell death discovery, 2023, 9(1): 60.
[5] Zuo Q, Liao L, Yao Z T, et al. Targeting PP2A with lomitapide suppresses colorectal tumorigenesis through the activation of AMPK/Beclin1-mediated autophagy[J]. Cancer Letters, 2021, 521: 281-293.
[6] Zhang H, Wang H, Hu Y, et al. Targeting PARP14 with lomitapide suppresses drug resistance through the activation of DRP1-induced mitophagy in multiple myeloma[J]. Cancer Letters, 2024, 588: 216802.
[7] Lee B, Park S J, Lee S, et al. Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR[J]. Cell death & disease, 2022, 13(7): 603.
[8] Zheng Y, Hu Y, Han Z, et al. Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration[J]. CNS neuroscience & therapeutics, 2022, 28(12): 2183-2194.
Lomitapide是一种微粒体甘油三酯转移蛋白（MTTP）抑制剂，IC50值为8nM[1]。Lomitapide通过靶向MTTP阻断肝脏和肠道中载脂蛋白B脂蛋白(Apo B)的组装[2]。Lomitapide目前已作为抗癌剂广泛应用于抑制肿瘤生长及开发新型联合疗法[3]。
在体外，Lomitapide处理72小时能显著抑制SW1990、AsPC-1和BxPC-3细胞增殖，IC50值分别为5.689μM、7.293μM和6.962μM[4]。使用2.5μM的Lomitapide处理HCT116细胞48小时，可显著抑制细胞活力，降低细胞内ATP水平，提高ROS含量，并促进细胞自噬[5]。用2μM的Lomitapide处理多发性骨髓瘤(MM)细胞24小时，能显著降低线粒体外膜通透性并诱导线粒体功能障碍[6]。
在体内，隔天腹腔注射20mg/kg剂量的Lomitapide连续10天，可显著抑制HCT116移植瘤在小鼠体内的生长，且不影响体重[7]。连续14天每日口服0.5mg/kg剂量的Lomitapide，能改善大脑中动脉阻塞(MCAO)小鼠的神经功能恢复，并减少神经组织损失[8]。
| Cell experiment [1]: | |
Cell lines | HCT116 cells |
Preparation Method | HCT116 cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and penicillin/streptomycin, and were placed in a incubator at 37°C and 5% CO2. The cells were exposed to the specified concentrations of Lomitapide (0, 1.25, 2.5, 5, and 10μM) for 24 hours, 48 hours and 72 hours. Add the WST-1 reagent and measure the absorbance value at a wavelength of 490nm. |
Reaction Conditions | 0, 1.25, 2.5, 5, and 10μM; 24, 48, and 72h |
Applications | Lomitapide treatment inhibited the cell viability of H1299 cells in a dose and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male BALB/c nude mice |
Preparation Method | HCT116 cells (2×106) were subcutaneously injected into 6-8 weeks old male BALB/c nude mice. When the average tumor volume reached 50mm3, the mice were randomly divided into two groups (n=6 each). The body weight and tumor diameter of the mice were measured every other day. Tumor volume was measured using a vernier caliper, and tumor volume was calculated according to the formula 0.5×(width)2×(length). Lomitapide treatment groups received 20mg/kg Lomitapide intraperitoneally for 10 days at 2-day intervals, and tumor tissues from mice were collected for analysis. |
Dosage form | 20mg/kg; every other day for 10 days; i.p. |
Applications | Lomitapide treatment significantly reduced tumor xenograft growth in mice without affecting body weight. |
References: | |
| Cas No. | 182431-12-5 | SDF | |
| 别名 | 洛美他派; AEGR-733; BMS-201038 | ||
| 化学名 | N-(2,2,2-trifluoroethyl)-9-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]piperidin-1-yl]butyl]fluorene-9-carboxamide | ||
| Canonical SMILES | C1CN(CCC1NC(=O)C2=CC=CC=C2C3=CC=C(C=C3)C(F)(F)F)CCCCC4(C5=CC=CC=C5C6=CC=CC=C64)C(=O)NCC(F)(F)F | ||
| 分子式 | C39H37F6N3O2 | 分子量 | 692.71 |
| 溶解度 | ≥ 22.4mg/mL in DMSO | 储存条件 | Store at -20°C, protect from light |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4436 mL | 7.218 mL | 14.4361 mL |
| 5 mM | 288.7 μL | 1.4436 mL | 2.8872 mL |
| 10 mM | 144.4 μL | 721.8 μL | 1.4436 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
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