[CAS NO. 135415-73-5] FL118
PRODUCTS SPECIFICATIONS [135415-73-5]
DESCRIPTION [135415-73-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 392.36 |
| Molecular Formula | C21H16N2O6 |
| SMILES | O=C1[C@](O)(CC)C(C=C2C3=NC4=CC5=C(C=C4C=C3CN2C6=O)OCO5)=C6CO1 |
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
DMSO : 2.5 mg/mL ( 6.37 mM ; ultrasonic and warming and heat to 60°C)
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 | --- | --- | --- |
References
- [1] Zhao H, et al. FL118, a novel anticancer compound, inhibits proliferation and migration of ovarian cancer cells via up-regulation of cytoglobin in vivo and in vitro[J]. Translational Cancer Research, 2017, 6(6):1294-1304.
- [2] Ling X, et al. FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy. Clin Transl Med. 2022 May;12(5):e881.
- [3] Wu G, et al. Synthesis of novel 10,11-methylenedioxy-camptothecin glycoside derivatives and investigation of their anti-tumor effects in vivo. RSC Adv. 2019 Apr 9;9(20):11142-11150.
- [4] Ling X, et, al. FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models. Am J Transl Res. 2015 Oct 15;7(10):1765-81.