| 产品介绍 |
FL118 (10,11-(Methylenedioxy)-20(S)-camptothecin)，一种喜树碱 (Camptothecin; HY-16560) 类似物，是一种口服有效的 survivin 抑制剂。FL118 与 DDX5 (p68) 结合，去磷酸化并降解 DDX5。FL118 可用于癌症的研究。
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| 生物活性 |
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.
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| 体外研究 |
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 h) dephosphorylates 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.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
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.
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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. |
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体内研究
(In Vivo) |
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[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 |
| T1/2 (hr) |
6.852 |
12.75 |
1.788 |
| Tmax (hr) |
0.167 |
0.167 |
0.167 |
| Cmax (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 |
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| 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 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. |
|
| 体内研究 |
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[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 |
| T1/2 (hr) |
6.852 |
12.75 |
1.788 |
| Tmax (hr) |
0.167 |
0.167 |
0.167 |
| Cmax (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 |
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| 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 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. |
|
|---|
| 体内研究 |
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[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 |
| T1/2 (hr) |
6.852 |
12.75 |
1.788 |
| Tmax (hr) |
0.167 |
0.167 |
0.167 |
| Cmax (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 |
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| 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 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. |
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| 性状 | Solid |
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| 溶解性数据 |
In Vitro:
DMSO : 2.5 mg/mL (6.37 mM; ultrasonic and warming and heat to 60°C)
配制储备液
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浓度
溶剂体积
质量
|
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 |
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*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
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4°C |
2 years |
| In solvent |
-80°C |
6 months |
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-20°C |
1 month |
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| 参考文献 |
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. 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.
. 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.
[Content Brief]
. 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.
[Content Brief]
[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.
[Content Brief]
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