FLI-06 Chemical Properties

Melting point:

199-202oC

Boiling point:

597.5±50.0 °C(Predicted)

Density 

1.25±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL, clear (warmed)

pka

0.78±0.70(Predicted)

form 

powder

color 

white to beige

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 week.

InChI

1S/C25H30N2O5/c1-15-21(24(29)32-18-7-5-4-6-8-18)22(16-9-11-17(12-10-16)27(30)31)23-19(26-15)13-25(2,3)14-20(23)28/h9-12,18,22,26H,4-8,13-14H2,1-3H3

InChIKey

SWWVFYHSSOWZMF-UHFFFAOYSA-N

SMILES

[N+](=O)([O-])c1ccc(cc1)C2C3=C(NC(=C2C(=O)OC4CCCCC4)C)CC(CC3=O)(C)C

Safety Information

RIDADR 

3077

WGK Germany 

3

HS Code 

29339900

Storage Class

11 - Combustible Solids

FLI-06 Usage And Synthesis

Description

FLI-06 (313967-18-9) was discovered in a screen designed to monitor the trafficking and processing of a ligand-independent Notch-enhanced GFP reporter. It was found to disrupt the Golgi apparatus in a manner distinct from that of brefeldin A. It inhibited general secretion at a step before exit from the ER which was accompanied by a tubule-to-sheet morphological transition of the ER. Thus FLI-06 is the first small molecule acting at such an early stage in secretory traffic.1

Uses

FLI-06 is a novel inhibitor of Notch signalling and the early secretory pathway.

Background

The dihydropyridine FLI-06 is a Notch pathway inhibitor with an EC50 of 2.5 mM. Signaling through Notch transmembrane receptor proteins plays an important role in cell-fate decisions; aberrant Notch activity can result in cancer and other developmental disorders. FLI-06 acts at an early stage in the secretory pathway, disrupting the Golgi and inhibiting general secretion before exit from the endoplasmic reticulum. Studies show that FLI-06 suppresses both the mRNA and protein expression of Notch receptor and Notch targeted genes. FLI-06 treatment of tongue cancer cells inhibits Notch signaling activation, decreasing cell proliferation, blocking cell cycle arrest, and inducing apoptosis. FLI-06 inhibited tumor growth and increased cell apoptosis in a xenograft mouse model, suggesting that FLI-06 is a potential chemotherapeutic agent for the clinical treatment of tongue tumors. Additional studies showed that FLI-06 inactivated Notch signaling and suppressed malignant functions in lung adenocarcinoma and esophageal squamous cell carcinoma.

References

[1] ANDREAS KRÄMER. Small molecules intercept Notch signaling and the early secretory pathway[J]. Nature chemical biology, 2013, 9 11: 731-738. DOI:10.1038/nchembio.1356

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