FLI-06 |
Catalog No.GC10211
One-Click Copy Product Info
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FLI-06 is a Notch signaling inhibitor (EC50 = 2.3µM) that acts upstream of α-secretase and β-secretase cleavage. FLI-06 disrupts intracellular trafficking and processing of the Notch signaling pathway, inhibiting general secretion at a stage prior to exiting the endoplasmic reticulum (ER) and transforming the ER morphology from tubules to lamellae. FLI-06 for the treatment of cancer and neurodegenerative diseases.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 313967-18-9
Sample solution is provided at 25 µL, 10mM.
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FLI-06 is a Notch signaling inhibitor (EC50 = 2.3µM) that acts upstream of α-secretase and β-secretase cleavage. FLI-06 disrupts intracellular trafficking and processing of the Notch signaling pathway, inhibiting general secretion at a stage prior to exiting the endoplasmic reticulum (ER) and transforming the ER morphology from tubules to lamellae. FLI-06 for the treatment of cancer and neurodegenerative diseases [1-4].
In ECa109 and EC9706 cells, FLI-06 (0, 2, 4, 8, 12, 14, 16, 18 and 20μM, 48h) blocked proliferation, induced apoptosis and G1 phase arrest of ESCC cells in a dose-dependent manner [5]. In CAL-27 and TCA-8113 cells, FLI-06 (0, 3, and 10μM, 48h) could block tongue cancer cell growth in a concentration-dependent manner [6]. In HNSCC cells, FLI-06 (10μM, 24h) affecting cells proliferation, growth and formation of HNSCC organoids, and effective inhibits Notch signaling in HNSCC cells [7]. In hepatocytes, FLI-06 (50μM, 24h) treatment abolished the Jagged-1-induced upregulation of NICD, p-Akt, HIF-1α, and cyclin E1 [8]. In mouse hippocampal NSCs, treatment with FLI-06 (20μM, 24h) inhibited the effects of CCN3 or shCCN3 on hippocampal NSC proliferation and neuronal differentiation [9]. In H1975 cells, ZFR-promoted migration and invasion in H1975 cells was abolished by FLI-06 (100nM, 1h) [10].
In CAL-27 xenograft mouse models, the tumor volume and tumor weight of the FLI-06 (40mg/kg, ip, 18d) treatment group were decreased compared with the control group [6]. In SD mouse, FLI-06 (3mg/kg, ip, 28d) inhibits liver regeneration after partial hepatectomy [11].
References:
[1]. Krämer A, Mentrup T, Kleizen B, et al. Small molecules intercept Notch signaling and the early secretory pathway. Nature chemical biology. 2013 Nov; 9(11): 731-738.
[2]. Yonemura Y, Li X, Müller K, et al. Inhibition of cargo export at ER exit sites and the trans-Golgi network by the secretion inhibitor FLI-06. Journal of Cell Science. 2016 Oct 15; 129(20): 3868-3877.
[3]. Gómez-Galeno JE, Hurtado C, Cheng J, et al. b-Annulated 1, 4-dihydropyridines as Notch inhibitors. Bioorganic & medicinal chemistry letters. 2018 Nov 1; 28(20): 3363-3367.
[4]. Yonemura Y, Li X, Müller K, et al. Inhibition of cargo export at ER exit sites and the trans-Golgi network by the secretion inhibitor FLI-06. Journal of Cell Science. 2016 Oct 15; 129(20): 3868-3877.
[5]. Lu Z, Ren Y, Zhang M, et al. FLI-06 suppresses proliferation, induces apoptosis and cell cycle arrest by targeting LSD1 and Notch pathway in esophageal squamous cell carcinoma cells. Biomedicine & Pharmacotherapy. 2018 Nov 1; 107: 1370-1376.
[6]. Gan RH, Lin LS, Xie J, et al. FLI-06 intercepts notch signaling and suppresses the proliferation and self-renewal of tongue cancer cells. OncoTargets and therapy. 2019 Sep 18: 7663-7674.
[7]. Czerwonka A, Kałafut J, Wang S, et al. The Notch inhibitor, FLI-06, increases the chemosensitivity of head and neck Squamous cell carcinoma cells to taxanes-based treatment. Biomedicine & Pharmacotherapy. 2024 Aug 1; 177: 116822.
[8]. Zhang F, Zhang J, Li X, et al. Notch signaling pathway regulates cell cycle in proliferating hepatocytes involved in liver regeneration. Journal of gastroenterology and hepatology. 2018 Aug; 33(8): 1538-1547.
[9]. Luan Y, Zhang H, Ma K, et al. CCN3/NOV regulates proliferation and neuronal differentiation in mouse hippocampal neural stem cells via the activation of the notch/PTEN/AKT pathway. International Journal of Molecular Sciences. 2023 Jun 19; 24(12): 10324.
[10]. Zhang H, Zhang CF, Chen R. Zinc finger RNA-binding protein promotes non-small-cell carcinoma growth and tumor metastasis by targeting the Notch signaling pathway. American Journal of Cancer Research. 2017 Sep 1; 7(9): 1804.
[11]. Li Y, Xu Y, Wang R, et al. Expression of Notch–Hif-1α signaling pathway in liver regeneration of rats. Journal of International Medical Research. 2020 Sep; 48(9): 0300060520943790.
| Cell experiment [1]: | |
Cell lines | ECa109 and EC9706 cells |
Preparation Method | ECa109 and EC9706 cells were seeded at density of 5 × 103 per well in 96-well plates, respectively. After incubated overnight, cells were treated with varying concentrations of FLI-06 (0, 2, 4, 8, 12, 14, 16, 18 and 20μM) for 48 h, and then 5μL CCK-8 reagents were added to each well. After cells were incubated in the 37 °C for 4h, the absorbance values of cells were measured using a microplate reader. |
Reaction Conditions | 0, 2, 4, 8, 12, 14, 16, 18 and 20μM; 48h |
Applications | FLI-06 inhibited cell proliferation in a dose-dependent manner in ECa109 and EC9706 cells. The IC50 values were (5.814 ± 0.053) and (10.741 ± 0.049)μM for ECa109 and EC9706 cells, respectively. |
| Animal experiment [2]: | |
Animal models | CAL-27 xenograft mouse models |
Preparation Method | The xenograft cancer nude mouse model was successfully established. Four days after the injection of CAL-27 cells, a daily intraperitoneal injection of FLI-06 at a dose of 40mg/kg body weight for nude mice was given, with administration for 6d and withdrawal for 2d, and treatment was stopped 2 cycles later. |
Dosage form | 40mg/kg; ip; 18d |
Applications | The tumor volume and tumor weight of the FLI-06 treatment group were decreased compared with the control group. |
References: | |
| Cas No. | 313967-18-9 | SDF | |
| Chemical Name | cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate | ||
| Canonical SMILES | CC1=C(C(C2=C(N1)CC(CC2=O)(C)C)C3=CC=C(C=C3)[N+](=O)[O-])C(=O)OC4CCCCC4 | ||
| Formula | C25H30N2O5 | M.Wt | 438.52 |
| Solubility | ≥ 16.1mg/mL in DMSO | 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 | 2.2804 mL | 11.402 mL | 22.804 mL |
| 5 mM | 456.1 μL | 2.2804 mL | 4.5608 mL |
| 10 mM | 228 μL | 1.1402 mL | 2.2804 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
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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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 2 reference(s) in Google Scholar.)