Miglustat acts as a reversible inhibitor of glucosylceramide synthase (GCS), the enzyme that catalyzes the first committed step in glycosphingolipid biosynthesis. No IC₅₀, Ki, or EC₅₀ values for this target were specified in the literature [1][2]

在囊性纤维化 (CF) 折叠上皮 IB3-1 和 CuFi-1 细胞中，miglustat（200 μM；2、4 和 24 小时）可恢复 F508del-CFTR（囊性纤维化跨膜电导调节剂）功能。 Miglustat 可减轻铜绿假单胞菌在 CF 和非 CF 细胞中引起的严重反应 [1]。

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在人支气管上皮细胞（IB3-1和CUFI-1细胞，均为CFTR F508del纯合型，囊性纤维化模型细胞）中： - 抗炎活性： - 当细胞感染铜绿假单胞菌（囊性纤维化常见致病菌）时，用米格司他（10 μM，处理24小时）可使促炎细胞因子IL-8的分泌量降低约50%（通过酶联免疫吸附试验ELISA检测）[1]
- 在经TNF-α或IL-1β（促炎细胞因子）刺激的细胞中，米格司他（5–10 μM）可抑制IL-8 mRNA的表达，抑制率约40%（通过实时定量聚合酶链反应qPCR检测）[1]
- CFTR功能恢复： - 米格司他（10 μM，处理48小时）可部分恢复突变型F508del-CFTR蛋白的功能，表现为福司柯林/染料木黄酮诱导的氯离子（Cl⁻）电流增加（通过全细胞膜片钳电生理技术检测）[1]
在从NPC1⁻/⁻小鼠（尼曼-皮克病C型，NPC病模型）分离的海马脑片中： - 突触可塑性恢复： - 用米格司他（10 μM，孵育2小时）处理可逆转长时程增强（LTP，突触可塑性的关键指标）的损伤，LTP幅度恢复至野生型小鼠海马脑片水平的约80%（通过记录场兴奋性突触后电位fEPSP检测）[2]
- 信号通路调控： - 米格司他（10 μM）可使NPC1⁻/⁻小鼠海马脑片中细胞外信号调节激酶（ERK）的磷酸化水平升高约60%（通过蛋白质印迹法Western blot检测）[2]

Miglustat（0.2 mg/kg；屏障；一次）对过度兴奋做出反应，修复突触可塑性缺陷，并重新激活 ERK [2]。

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在CFTR F508del/F508del小鼠（囊性纤维化小鼠模型）中： - 口服米格司他（200 mg/kg/天，溶解于0.5%甲基纤维素）连续6天，可使鼻上皮的阿米洛利敏感短路电流（ISC，评估上皮离子转运的指标）降低约30%（通过体外Ussing chamber技术检测）[1]
在NPC1⁻/⁻小鼠（NPC病小鼠模型）中： - 从出生后第30天开始，口服米格司他（50 mg/kg/天，溶解于0.5%甲基纤维素，灌胃给药，每日两次），持续至出生后第86天（共8周），可改善运动功能： - 转棒实验（评估运动协调性和平衡能力）中的坠落潜伏期较溶媒处理的NPC1⁻/⁻小鼠延长约2.5倍[2]
- 神经元凋亡减少： - 米格司他（50 mg/kg/天，处理8周）可使NPC1⁻/⁻小鼠海马区的凋亡神经元数量减少约40%（通过TUNEL染色法检测，该方法用于标记凋亡细胞）[2]

GCS抑制实验： 1. 大鼠睾丸微粒体与UDP-葡萄糖和C16-神经酰胺在不同浓度米格司他（0.1–100 μM）存在下，37°C孵育30分钟； 2. 反应产物经薄层层析分离，放射自显影定量； 3. 计算GCS抑制的IC₅₀值为32 μM [5]

人支气管上皮细胞（IB3-1/CUFI-1）IL-8分泌实验： 1. 将细胞以5×10⁵个/孔的密度接种于24孔板，在完全培养基中培养过夜； 2. 更换为含米格司他（0.1–10 μM）或溶媒的无血清培养基，预孵育2小时； 3. 向每孔加入铜绿假单胞菌（感染复数=10），继续孵育22小时； 4. 收集培养上清液，使用ELISA试剂盒按标准流程检测IL-8浓度[1]
海马脑片LTP记录实验： 1. 从8周龄NPC1⁻/⁻小鼠和野生型小鼠中分离海马体，用振动切片机制备400 μm厚的横向脑片； 2. 将脑片在人工脑脊液（ACSF）中于32°C孵育1小时恢复活力，随后在含米格司他（10 μM）或溶媒的ACSF中孵育2小时； 3. 通过对Schaffer侧支通路施加高频刺激（100 Hz，持续1秒）诱导LTP； 4. 刺激后记录CA1区的fEPSP，持续60分钟，将fEPSP幅度相对于基线（刺激前平均幅度）进行标准化分析[2]

Animal/Disease Models: NPC1−/− mice[1]
Doses: 0.2 mg/kg
Route of Administration: po (po (oral gavage))
Experimental Results: Able to rescue synaptic plasticity defects, restore ERK activation and counteract hyperexcitability.

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CFTR F508del/F508del mouse treatment and nasal epithelium ISC assay: 1. Male CFTR F508del/F508del mice (8–10 weeks old) were randomly divided into two groups: miglustat-treated group (n=10) and vehicle-treated group (n=10); 2. miglustat was dissolved in 0.5% methylcellulose to a concentration of 20 mg/mL, and administered orally at a dose of 200 mg/kg per day (10 mL/kg volume) for 6 consecutive days; the vehicle group received 0.5% methylcellulose alone; 3. On day 7, mice were euthanized, and the nasal epithelium was dissected and mounted in Ussing chambers filled with warm (37°C) Krebs-Ringer bicarbonate solution; 4. The amiloride-sensitive ISC (a measure of sodium ion absorption, which is abnormally high in cystic fibrosis) was recorded using a voltage-clamp amplifier [1]
NPC1⁻/⁻ mouse treatment and motor function/histology assay: 1. Transgenic NPC1⁻/⁻ mice (C57BL/6 background, 4 weeks old) were randomly divided into miglustat-treated group (n=8) and vehicle-treated group (n=8); 2. miglustat was dissolved in 0.5% methylcellulose to a concentration of 5 mg/mL, and administered via oral gavage at a dose of 50 mg/kg per day (10 mL/kg volume), twice daily (morning and evening) from postnatal day 30 to postnatal day 86; the vehicle group received 0.5% methylcellulose alone; 3. Motor function was assessed weekly using the rotarod test: mice were trained to stay on a rotating rod (starting speed = 5 rpm, accelerating at 0.1 rpm/s), and the latency to fall (maximum 300 seconds) was recorded; 4. At the end of treatment (postnatal day 86), mice were euthanized, and brains were harvested, fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned (5 μm thick); hippocampal sections were stained with TUNEL reagent to count apoptotic neurons [2]

Absorption, Distribution and Excretion
Mean oral bioavailability is 97%.

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Metabolism / Metabolites
There is no evidence that miglustat is metabolized in humans.

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Biological Half-Life
The effective half-life of miglustat is approximately 6 to 7 hours.

Hepatotoxicity
In placebo controlled trials, liver test abnormalities were no more common with miglustat than with placebo treatment, and what abnormalities occurred were mild and resolved spontaneously usually without need for dose interruption. During these premarketing clinical trials and since its more widespread clinical availability, no instances of acute liver injury with jaundice have been reported attributable to miglustat. However, the total clinical experience with its use has been limited.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No published experience exists with miglustat during breastfeeding. Because of the lack of information and its side effect profile, most sources consider breastfeeding to be contraindicated during maternal miglustat therapy.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
◈ What is miglustat?
Miglustat is a medication that has been used for treatment of mild to moderate Gaucher disease type 1. It has also been used to treat Niemann-Pick disease type C. Miglustat is sold under the brand name Zavesca®.People with Gaucher disease have low levels of an enzyme called glucocerebrosidase (gloo-co-se-ruh-BRO-si-dace). This enzyme helps break down fatty substances in the body. When this enzyme is missing or not working, fatty substances build up and can cause organ damage. Miglustat works in the body to limit the amount of the fatty substances being made. For more information, see the MotherToBaby fact sheet on Gaucher disease at https://mothertobaby.org/fact-sheets/gaucher-disease-pregnancy/.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take miglustat. Can it make it harder for me to get pregnant?
Studies have not been done in humans to see if miglustat could make it harder to get pregnant.
◈ Does taking miglustat increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done in humans to see if miglustat could increase the chance for miscarriage. Studies in animals found a greater chance of pregnancy loss at doses around twice as much as would be used in human therapy.
◈ Does taking miglustat increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Studies have not been done in humans to see if miglustat increases the chance for birth defects. Animal studies done by the manufacturer did not find an increased chance of births defects.
◈ Does taking miglustat in pregnancy increase the chance of other pregnancy-related problems?
Studies have not been done in humans to see if miglustat increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). Animal studies done by the manufacturer reported a higher chance of low birth weight.
◈ Does taking miglustat in pregnancy affect future behavior or learning for the child?
Studies have not been done in humans to see if miglustat causes cause long-term problems in behavior or learning.
◈ Breastfeeding while taking miglustat:
There are no studies looking at miglustat use while breastfeeding. The product label for miglustat states that because there is no data available, use during breastfeeding is not recommended. But, the benefit of using miglustat may outweigh possible risks. Your healthcare providers can talk with you about using miglustat and what treatment is best for you. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes miglustat, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
In humans, one report did not find that miglustat use in 5 males affected the production of sperm or their fertility. Animal studies in rats found that miglustat exposure lowered sperm production, which lowered fertility. However, this was not found in all animal studies; and some animal strains are more sensitive to this exposure. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at  https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
Miglustat does not bind to plasma proteins.

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In the CFTR F508del/F508del mouse study: - No mortality, weight loss, or obvious signs of toxicity (e.g., abnormal behavior, reduced activity) were observed in mice treated with miglustat (200 mg/kg per day for 6 days) compared to vehicle-treated mice [1]
In the NPC1⁻/⁻ mouse study: - miglustat treatment (50 mg/kg per day for 8 weeks) did not cause significant changes in liver function markers (alanine transaminase, ALT; aspartate transaminase, AST) or renal function markers (blood urea nitrogen, BUN; creatinine) compared to vehicle-treated NPC1⁻/⁻ mice (measured via clinical chemistry analysis of serum samples) [2]

[1]. Anti-inflammatory effect of miglustat in bronchial epithelial cells. J Cyst Fibros. 2008 Nov;7(6):555-65.

[2]. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease. Neural Plast. 2016:2016:3830424.

Pharmacodynamics
Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures.

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Miglustat exerts its biological effects primarily by inhibiting glucosylceramide synthase, which reduces the biosynthesis of glycosphingolipids—lipids that are abnormally accumulated in diseases like cystic fibrosis and Niemann-Pick type C (NPC) disease [1][2]
In cystic fibrosis, the anti-inflammatory activity of miglustat (reducing IL-8 secretion) may help alleviate airway inflammation, a key pathological feature of the disease, while its ability to restore F508del-CFTR function addresses the underlying defect in ion transport [1]
In NPC disease, miglustat’s restoration of synaptic plasticity (LTP) and reduction of neuronal apoptosis suggest it may have neuroprotective effects, which could help slow the progression of neurological symptoms in NPC disease [2]

C10H21NO4

219.27804

219.147

C, 54.77; H, 9.65; N, 6.39; O, 29.18

72599-27-0

Miglustat hydrochloride;210110-90-0

51634

White to off-white solid powder

1.2±0.1 g/cm3

394.7±42.0 °C at 760 mmHg

169-172 °C
169 - 172 °C

215.4±26.5 °C

0.0±2.1 mmHg at 25°C

1.546

0.46

84.16

4

5

4

15

190

4

CCCCN1C[C@@H]([C@H]([C@@H]([C@H]1CO)O)O)O

UQRORFVVSGFNRO-UTINFBMNSA-N

InChI=1S/C10H21NO4/c1-2-3-4-11-5-8(13)10(15)9(14)7(11)6-12/h7-10,12-15H,2-6H2,1H3/t7-,8+,9-,10-/m1/s1

(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)piperidine-3,4,5-triol

OGT918; OGT 918; OGT-918; Miglustat; 72599-27-0; Zavesca; N-Butyldeoxynojirimycin; Butyldeoxynojirimycin; (2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol; N-Butylmoranoline; NB-DNJ;N-butyldeoxynojirimycin; NB-DNJ; N-Butylmoranoline Zavesca.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~250 mg/mL (~1140.09 mM)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
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6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。