Kifunensine (Synonyms: FR900494) |
| رقم الكتالوجGC17735 |
مثبط لألفا-مانوزيدازات الصنف الأول الذي يعيق معالجة الجليكوبروتينات.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 109944-15-2
Sample solution is provided at 25 µL, 10mM.
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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.
| 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: | |
| Cas No. | 109944-15-2 | SDF | |
| المرادفات | FR900494 | ||
| Chemical Name | (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 | ||
| Formula | C8H12N2O6 | M.Wt | 232.19 |
| الذوبان | DMSO : 11.9 mg/mL (51.25 mM; Need ultrasonic);0.5mg/mL in warm distilled water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)
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