Home>>Signaling Pathways>> Others>> Saccharides and Glycosides>>Kifunensine

Kifunensine

(Synonyms: 几夫碱,FR900494) 目录号 : GC17735

Kifunensine(FR900494)是一种有效的甘露糖苷酶I抑制剂,能够有效抑制内质网α-1,2-甘露糖苷酶I(MAN1B1)和I类甘露糖苷酶高尔基体亚家族(高尔基体α-甘露糖苷酶IA、IB和IC)的活性,Ki值分别为130和23nM。Kifunensine还抑制绿豆 α-1,2-甘露糖苷酶I,IC50 值为20-50nM。

Kifunensine Chemical Structure

Cas No.:109944-15-2

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥2,970.00
现货
1mg
¥1,220.00
现货
5mg
¥2,700.00
现货
10mg
¥4,320.00
现货
25mg
¥8,640.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

Description

Kifunensine (FR900494) is a potent mannosidase I inhibitor that effectively inhibits the activities of endoplasmic reticulum α-1,2-mannosidase I (MAN1B1) and class I mannosidase Golgi subfamily (Golgi α-mannosidase IA, IB, and IC) with Ki values ​​of 130 and 23 nM, respectively. Kifunensine also inhibits mung bean α-1,2-mannosidase I with IC50 values of 20-50 nM [1, 2]. Kifunensine inhibits the endoplasmic reticulum-associated degradation (ERAD) pathway and prevents glycosylation trimming of misfolded glycoproteins [3].

In vitro, kifunensine (1, 10, 50 µM) treatment of OVCAR8 cells for 72 h strongly inhibited spheroid formation at a low concentration of 1 μM and dose-dependently induced mass shift of the N-glycosylated adhesion molecule ALCAM protein in the cells, causing the protein to accumulate in the cytoplasm[4]. Kifunensine (10 µM) treatment of MDA-MB-231 and T47D cells for 48 h resulted in mass transfer of N-glycosylated adhesion molecules ALCAM, ICAM-1, and BCAM[5]. Kifunensine (20 μg/mL) treatment of mesenchymal stromal cells (MSCs) induced an increase in angiopoietin 2 levels and significantly increased cell proliferation when cultured for up to six days[6].

In vivo, oral treatment of triptan knockout mice with kifunensine (4 mg/kg) for 12 days increased the expression level of calcium chelator 2 (CSQ2) to 117% ± 32% and reversed electrocardiographic abnormalities[7].

References:
[1] Soheili T, Gicquel E, Poupiot J, et al. Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications[J]. Human mutation, 2012, 33(2): 429-439.
[2] Bartoli M, Gicquel E, Barrault L, et al. Mannosidase I inhibition rescues the human α-sarcoglycan R77C recurrent mutation[J]. Human molecular genetics, 2008, 17(9): 1214-1221.
[3] Seidel E, Dassa L, Kahlon S, et al. A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain[J]. Nature communications, 2021, 12(1): 2061.
[4] Hamester F, Legler K, Wichert B, et al. Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation[J]. British Journal of Cancer, 2019, 121(11): 944-953.
[5] Legler K, Rosprim R, Karius T, et al. Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer[J]. British journal of cancer, 2018, 118(6): 847-856.
[6] Alonso-Garcia V, Chaboya C, Li Q, et al. High mannose N-glycans promote migration of bone-marrow-derived mesenchymal stromal cells[J]. International journal of molecular sciences, 2020, 21(19): 7194.
[7] Cacheux M, Fauconnier J, Thireau J, et al. Interplay between triadin and calsequestrin in the pathogenesis of CPVT in the mouse[J]. Molecular Therapy, 2020, 28(1): 171-179.

Kifunensine(FR900494)是一种有效的甘露糖苷酶I抑制剂,能够有效抑制内质网α-1,2-甘露糖苷酶I(MAN1B1)和I类甘露糖苷酶高尔基体亚家族(高尔基体α-甘露糖苷酶IA、IB和IC)的活性,Ki值分别为130和23nM。Kifunensine还抑制绿豆 α-1,2-甘露糖苷酶I,IC50 值为20-50nM[1, 2]。Kifunensine可抑制内质网相关降解(ERAD)途径,防止错误折叠糖蛋白的糖基化修剪[3]

在体外,Kifunensine(1,10,50µM)处理OVCAR8细胞72h,在低浓度1μM下强烈抑制球状体的形成,剂量依赖性地导致细胞中N-糖基化粘附分子ALCAM蛋白发生了质量转移,使该蛋白质在细胞质中积累[4]。Kifunensine(10µM)处理MDA-MB-231和T47D细胞48h,N-糖基化粘附分子ALCAM、ICAM-1和BCAM均发生了质量转移[5]。Kifunensine(20 μg/mL)处理间充质基质细胞(MSC),诱导血管生成素2水平增加,在连续培养长达六天时细胞增殖显著增加[6]

在体内,Kifunensine(4mg/kg)通过口服治疗三联蛋白敲除小鼠12天,提高了钙螯合蛋白2(CSQ2)表达水平,使其增加至117%±32%,逆转了心电图异常[7]

实验参考方法

Cell experiment [1]:

Cell lines

OVCAR8 cells

Preparation Method

OVCAR8 cells were incubated with mannosidase inhibitor kifunensine in three different concentrations (1, 10 and 50 µM) for 72h in serum-reduced medium (5% (v/v) FCS), and functional assays were subsequently performed.

Reaction Conditions

1, 10 and 50 µM; 72h

Applications

Treatment with kifunensine strongly inhibits OVCAR8 spheroid formation already at low concentration (1 µM).
Animal experiment [2]:

Animal models

Two-week-old triadin KO male mice

Preparation Method

Two-week-old triadin KO male mice (5–7 g) were injected intraperitoneally with 1.5×1011 viral genome copies diluted in 100μL. The mice were used after 6 weeks of transgene expression. Kifunensine was diluted at 0.8 mg/mL in water, and the mice were treated daily by gastric feeding at 4 mg/kg/day for the last 12 days before experiments.

Dosage form

4mg/kg; p.o.

Applications

Kifunensine treatment in triadin KO mice increased CSQ2 expression to 117% ± 32%.

References:
[1] Hamester F, Legler K, Wichert B, et al. Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation[J]. British Journal of Cancer, 2019, 121(11): 944-953.
[2]Cacheux M, Fauconnier J, Thireau J, et al. Interplay between triadin and calsequestrin in the pathogenesis of CPVT in the mouse[J]. Molecular Therapy, 2020, 28(1): 171-179.

化学性质

Cas No. 109944-15-2 SDF
别名 几夫碱,FR900494
化学名 (hexahydro-6R,7S,8aS-trihydroxy-5R-(hydroxymethyl)-imidazo[1,2-a]pyridine-2,3-dione
Canonical SMILES VO[C@@H]([C@H]1O)[C@@H](NC2=O)N(C2=O)[C@H](CO)[C@H]1O
分子式 C8H12N2O6 分子量 232.19
溶解度 DMSO : 11.9 mg/mL (51.25 mM; Need ultrasonic);0.5mg/mL in warm distilled water 储存条件 Store at -20°C
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。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 4.3068 mL 21.5341 mL 43.0682 mL
5 mM 0.8614 mL 4.3068 mL 8.6136 mL
10 mM 0.4307 mL 2.1534 mL 4.3068 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

产品文档

Quality Control & SDS

View current batch: