product name FLI-06
Description: FLI-06 is a novel and potent inhibitor of Notch signaling with EC50 of 2.3 μM. FLI-06 disrupts the Golgi apparatus in a manner distinct from that of brefeldin A and golgicide A. FLI-06 inhibits general secretion at a step before exit from the endoplasmic reticulum (ER), which was accompanied by a tubule-to-sheet morphological transition of the ER. FLI-06 is the first small molecule acting at such an early stage in secretory traffic. Notch signaling has a pivotal role in numerous cell-fate decisions, and its aberrant activity leads to developmental disorders and cancer.
References: Nat Chem Biol. 2013 Nov;9(11):731-8.
438.52
Formula
C25H30N2O5
CAS No.
313967-18-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: 8 mg/mL (18.2 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19422393
| In Vitro |
In vitro activity:In HeLa NotchΔE-eGFP cells, FLI-06 blocks Notch trafficking and processing. FLI-06 changes the maturation pattern of APP and abolishes the shedding of APPs in HEK293 cells stably expressing a mutated APP that yields robust amounts of amyloid β. FLI-06 disrupt the Golgi apparatus, and inhibits general secretion at a step before exit from the endoplasmic reticulum (ER), which is accompanied by a tubule-to-sheet morphological transition of the ER. Kinase Assay: Cell Assay: Treatment of HeLa NotchΔE-eGFP cells with FLI-06 resulted in accumulation of NotchΔE-eGFP and reduced NICD-eGFP production. The phenotype was fully reversible within 1–4 h when washing out of FLI-06, which indicated that FLI-06 is not acutely toxic in cells [1]. In FLI-06 treated cells, Aβ secretion reduced significantly but not APPCTF accumulation, suggesting that FLI-06 acts upstream of α-secretase and β-secretase cleavage. Immunofluorescence analysis of HeLa cells revealed that FLI-06 caused a complete disruption of the Golgi, which can be caused by interfering with membrane trafficking in the early secretory pathway or by disassembly of the microtubules17. FLI-06 inhibited ER exit and also elicited the tubule-to-sheet phenotype, which are related to each other |
|---|---|
| In Vivo | FLI-06 (50 μM) inhibits endogenous Notch signaling in zebrafish embryos. |
| Animal model | |
| Formulation & Dosage | |
| References | Nat Chem Biol. 2013 Nov;9(11):731-8. |
