[CAS NO. 135415-73-5]  FL118

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PRODUCTS SPECIFICATIONS [135415-73-5]

Catelog
HY-12486
Brand
MCE
CAS
135415-73-5

DESCRIPTION [135415-73-5]

Overview

MDL-
Molecular Weight392.36
Molecular FormulaC21H16N2O6
SMILESO=C1[C@](O)(CC)C(C=C2C3=NC4=CC5=C(C=C4C=C3CN2C6=O)OCO5)=C6CO1

For research use only. We do not sell to patients.

Summary

FL118 (10,11-(Methylenedioxy)-20(S)-camptothecin), a Camptothecin (HY-16560) analogue, is a potent and orally active survivin inhibitor. FL118 binds to oncoprotein DDX5 (p68) to dephosphorylates and degrades DDX5. FL118 can be used for the research of cancer [1] [2] .


In Vitro

FL118 (0-200 nM; 24, 48 and 72 h ) inhibits the cell proliferation of ES-2 and SK-O-V 3 cells [1] .
FL118 (0-100 nM; 0 and 24 h) inhibits the migration of ES-2 and SK-O-V 3 cells [1] .
FL118 (0-100 nM; 48 h) affects the expression level of cytoglobin (CYGB) [1] .
FL118 (10 and 100 nM; 48 h) inhibits PI3K/AKT/mTOR signaling pathway, and affects the expression level of vimentin and E-cadherin in ovarian cancer cells [1] .
FL118 (0-100 nM; 6 and 24 h) dephosphorylates and degrades DDX5 [2] .
FL118 (0-500 nM; 24, 48, 72 h) regulates survivin, McL-1, XIAP, cIAP2, c-MYc and mKras by regulating DDX5 [2] .
FL118 (0-1 μM, 24 h) shows significant cytotoxic activity against the three tumor cell lines (A549, MDA-MB-231, and RM-1 cells) [3] .
FL118 (0-10 nM, 48 h) increases the production of PARP cleavage, and induces apoptosis in A549 [3] .
FL118 (0-10 nM, 48 h) arrests A549 cells mainly at the G2/M phase [3] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis [1]

Cell Line: ES-2 and SK-O-V 3 cell lines
Concentration: 10 and 100 nM
Incubation Time: 48 h
Result: Effectively inhibited the activation of PI3K/AKT/mTOR signaling pathway in ovarian cancer cells and also inhibited the migration of ES-2 and SK-O-V 3 cells.

Cell Migration Assay [1]

Cell Line: ES-2 and SK-O-V 3 cell lines
Concentration: 0, 10 and 100 nM
Incubation Time: 0 and 24 h
Result: Inhibited the migration of ES-2 and SK-O-V 3 cells dose-dependenly.

RT-PCR [1]

Cell Line: ES-2 and SK-O-V 3 cell lines
Concentration: 0, 10 and 100 nM
Incubation Time: 48 h
Result: Promoted CYGB expression.

Cell Proliferation Assay [1]

Cell Line: ES-2 and SK-O-V 3 cell lines
Concentration: 0, 1, 10, 50, 100 and 200 nM
Incubation Time: 24, 48 and 72 h
Result: Inhibited the cell proliferation of ES-2 and SK-O-V 3 cells time- and dose-dependently.

Western Blot Analysis [2]

Cell Line: SW620 and Mia Paca-2
Concentration: 0, 10 and 100 nM
Incubation Time: 6 and 24 h
Result: Induced dephosphorylation of DDX5 through the ubiquitin-proteasome degradation pathway and degraded DDX5 time-dependently.

Western Blot Analysis [2]

Cell Line: PDAC Panc1, CRC HCT-8, SW620, Mia Paca-2, Panc-1, HCT-8 cell lines
Concentration: 0, 10, 100 and 500 nM
Incubation Time: 24, 48, 72 h
Result: Controled the expression of survivin, Mcl-1, XIAP, cIAP2, c-Myc and mKras by regulated DDX5, as an upstream master regulator in cancer development and malignant networks.

Cell Cytotoxicity Assay [3]

Cell Line: A549, MDA-MB-231, RM-1
Concentration: 0-1 μM
Incubation Time: 24 h
Result: Showed cytotoxicity in A-549 (human lung carcinoma), MDA-MB-231 (human breast carcinoma) and RM-1 (mouse prostate carcinoma), with IC 50 values of 8.94 ± 1.54 , 24.73 ± 13.82, and 69.19 ± 8.34 nM, respectively.

Apoptosis Analysis [3]

Cell Line: A549 cells
Concentration: 0, 2.5, 5, 10 nM
Incubation Time: 48 h
Result: Resulted in the downregulation of survivin. Increased the production of PARP cleavage in a concentration-dependent manner, which is the hallmark of apoptosis. Induced apoptosis in A549.

Cell Cycle Analysis [3]

Cell Line: A549 cells
Concentration: 0, 2.5, 5, 10 nM
Incubation Time: 48 h
Result: Increased G2/M cell population in a concentration-dependent manner, and arrested A549 cells mainly at the G2/M phase.

In Vivo

FL118 (5 and 10 mg/kg; p.o. once a week for 20 days) inhibits antitumor activity [1] .
FL118 (0-1.5 mg/kg, i.p. once every other day for five times) effectively eliminates human colon and head-and-neck tumors that acquire irinotecan or topotecan resistance [4] .
FL118 (1.5 mg/kg, i.v. once) exhibits favorable pharmacokinetics profiles [4] .
Pharmacokinetic Parameters of FL118 in female SCID mice [4] .

Sample FaDu SW620 Plasma
T 1/2 (hr) 6.852 12.75 1.788
T max (hr) 0.167 0.167 0.167
C max (ng/g, mL) 115 158 43
AUC (hr*ng/g) 413 842 82
AUC (hr*ng/g) 448 897 104
AUC% Extrap (%) 7.74 6.17 21.7
Vz (g/kg) (ml/kg) 33052 30742 36849
Cl (g/hr/kg) (ml/hr/kg) 3343 1671 14287

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Fmale BALB/c nude mice [1]
Dosage: 5 and 10 mg/kg
Administration: Oral gavage; 5 mg/kg for once a week; 10 mg/kg for once a week; for 20 days
Result: Showed better antitumor activity than topotecan and dose-dependenly suppressed the growth of ES-2 tumors by upregulating the expression level of CYGB.
Animal Model: SCID (severe combined immunodeficiency) mice bearing human SW620 (colon) and FaDu (head-and-neck) xenograft tumors (ten-week-old, female, 20-25 g, 5 mice per cage) [4]
Dosage: 0, 0.75, 1, 1.5 mg/kg
Administration: IP, once every other day for five times as one cycle (If tumors relapse, mice were treated with FL118 for second or third cycles)
Result: Eliminated human xenograft tumors that acquired irinotecan or topotecan resistance, and was also effective after multiple cycles of treatment without the generation of FL118 resistance.
Animal Model: SCID (severe combined immunodeficiency) mice bearing human SW620 (colon) and FaDu SCID mice bearing human SW620 (colon) and FaDu (head-and-neck) xenograft tumors (ten-week-old, female, 20-25 g, 5 mice per cage) [4]
Dosage: 1.5 mg/kg
Administration: IV, once
Result: Exhibited favorable pharmacokinetics profiles.

Appearance

Solid


Shipping

Room temperature in continental US; may vary elsewhere.


Storage

Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month

Solvent & Solubility

In Vitro:

DMSO : 2.5 mg/mL ( 6.37 mM ; ultrasonic and warming and heat to 60°C)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.5487 mL 12.7434 mL 25.4868 mL
5 mM 0.5097 mL 2.5487 mL 5.0974 mL
10 mM --- --- ---
* Please refer to the solubility information to select the appropriate solvent.