- Cart - 0 item(s)
- $0.00
Your shopping cart is empty!
- Chemistry
- Bioactive Molecules
- Anti-infection
- Apoptosis
- Autophagy
- Cell Cycle/DNA Damage
- Cytoskeleton
- Epigenetics
- GPCR/G Protein
- Immunology/Inflammation
- JAK/STAT Signaling
- MAPK/ERK Pathway
- Membrane Transporter/Ion Channel
- Metabolic Enzyme/Protease
- Neuronal Signaling
- NF-κB
- PI3K/Akt/mTOR
- PROTAC
- Protein Tyrosine Kinase/RTK
- Stem Cell/Wnt
- TGF-beta/Smad
- Vitamin D Related/Nuclear Receptor
- Others
- Methylation
- Cytoskeletal Signaling
- Natural Products
- Alkaloids
- Amino acid
- Anthraquinones
- Cerebrosides
- Chalcones
- Coumarins
- Diterpenoids
- Flavonoids
- Iridoids
- Lignans
- Lipids
- Miscellaneous
- Monoterpenoids
- Other terpenes
- Phenols
- Phenylpropanoids
- Quinones
- Saccharides
- Sesquiterpenoids
- Steroids
- Tetraterpenoids
- Thiophenes
- Triterpenoids
- Xanthones
- Polyphenols
- Stibene glucosides
- Oligose
- Anthocyanins
- Miscellaneous
- Chromones
- Terpenoids
- Indoles
- Procyanidins
- Aliphatics
- Botanical Cyclopeptides
- ADCs
- Antibodies
- Multiplex IHC
- Material Science
- Others
[CAS NO. 135415-73-5] FL118
| Ships within | Stock | Price | Qty | Total |
Please click "REQUEST A QUOTE" button if there is no stock, or you need other sizes or custom synthesis.
| Catalog: | HY-12486 |
| Brand: | MCE |
| CAS: | 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.
Arctom is a premier supply platform offering over 600K unique items of Building Blocks, Bioactive Molecules, Natural Products, ADC PEG Linkers, Antibodies, and other Research Chemicals for global pharmaceutical, biotech, university, and industrial customers. We accelerate your research by providing better and faster purchasing experience & services.