FL118

Research use only, not for human use.

FL118 is a novel survivin inhibitor that inhibits cancer stem cell-like properties.FL118 is a novel camptothecin analog with anticancer activity that inhibits epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway, thereby inhibiting migration and invasion of human breast cancer cells.

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.

FL118 (0-200 nM; 24, 48 and 72 h ) inhibits the cell proliferation of ES-2 and SK-O-V3 cells.FL118 (0-100 nM; 0 and 24 h) inhibits the migration of ES-2 and SK-O-V3 cells.FL118 (0-100 nM; 48 h) affects the expression level of cytoglobin (CYGB).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.FL118 (0-100 nM; 6 and 24 hdephosphorylates and degrades DDX5.FL118 (0-500 nM; 24, 48, 72 h) regulates survivin, McL-1, XIAP, cIAP2, c-MYc and mKras by regulating DDX5.FL118 (0-1 μM, 24 h) shows significant cytotoxic activity against the three tumor cell lines (A549, MDA-MB-231, and RM-1 cells).FL118 (0-10 nM, 48 h) increases the production of PARP cleavage, and induces apoptosis in A549.FL118 (0-10 nM, 48 h) arrests A549 cells mainly at the G2/M phase.Western Blot Analysis Cell Line:ES-2 and SK-O-V3 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-V3 cells.Cell Migration Assay Cell Line:ES-2 and SK-O-V3 cell lines Concentration:0, 10 and 100 nM Incubation Time:0 and 24 h Result:Inhibited the migration of ES-2 and SK-O-V3 cells dose-dependenly.RT-PCR Cell Line:ES-2 and SK-O-V3 cell lines Concentration:0, 10 and 100 nM Incubation Time:48 h Result:Promoted CYGB expression.Cell Proliferation Assay Cell Line:ES-2 and SK-O-V3 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-V3 cells time- and dose-dependently.Western Blot Analysis 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 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 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 IC50 values of 8.94 ± 1.54, 24.73 ± 13.82, and 69.19 ± 8.34 nM, respectively.Apoptosis Analysis 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 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.

FL118 (5 and 10 mg/kg; p.o. once a week for 20 days) inhibits antitumor activity.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.FL118 (1.5 mg/kg, i.v. once) exhibits favorable pharmacokinetics profiles.Pharmacokinetic Parameters of FL118 in female SCID mice.Animal Model:Fmale BALB/c nude mice 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 daysResult: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) 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) Dosage:1.5 mg/kg Administration:IV, once Result:Exhibited favorable pharmacokinetics profiles.

——

Others

Other Targets

Survivin

——

——

135415-73-5

392.36

C21H16N2O6

>98% (HPLC)

In Vitro:?DMSO : 1 mg/mL (2.55 mM; Ultrasonic (<60°C)

C(C)[C@]1(O)C2=C(C(=O)N3C(=C2)C=4C(C3)=CC=5C(N4)=CC6=C(C5)OCO6)COC1=O

——

(-20℃)

With Ice Pack

≥ 2 years