10,11-methylenedioxycamptothecin

Modify Date: 2024-01-22 20:51:12

10,11-methylenedioxycamptothecin Structure
10,11-methylenedioxycamptothecin structure
Common Name 10,11-methylenedioxycamptothecin
CAS Number 135415-73-5 Molecular Weight 392.36200
Density 1.64g/cm3 Boiling Point 812.1ºC at 760mmHg
Molecular Formula C21H16N2O6 Melting Point N/A
MSDS N/A Flash Point 445ºC

 Use of 10,11-methylenedioxycamptothecin


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].

 Names

Name Mdo-cpt
Synonym More Synonyms

 10,11-methylenedioxycamptothecin Biological Activity

Description 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].
Related Catalog
In Vitro FL118 (0-200 nM; 24, 48 and 72 h ) inhibits the cell proliferation of ES-2 and SK-O-V3 cells[1]. FL118 (0-100 nM; 0 and 24 h) inhibits the migration of ES-2 and SK-O-V3 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) can dephosphorylate and degrade 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]. Western Blot Analysis[1] 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 [1] 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[1] 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[1] 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[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 IC50 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.
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.

 Chemical & Physical Properties

Density 1.64g/cm3
Boiling Point 812.1ºC at 760mmHg
Molecular Formula C21H16N2O6
Molecular Weight 392.36200
Flash Point 445ºC
Exact Mass 392.10100
PSA 99.88000
LogP 1.80830

 Safety Information

Hazard Codes Xn

 Synthetic Route

~83%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Wall, Monroe E.; Wani, Mansukh C.; Nicholas, Allan W.; Manikumar, Govindarajan; Tele, Chhagan; et al. Journal of Medicinal Chemistry, 1993 , vol. 36, # 18 p. 2689 - 2700

~78%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

~%

10,11-methylenedioxycamptothecin Structure

10,11-methylene...

CAS#:135415-73-5

Literature: Josien, Hubert; Ko, Sung-Bo; Bom, David; Curran, Dennis P. Chemistry - A European Journal, 1998 , vol. 4, # 1 p. 67 - 83

 Synonyms

10H-1,3-Dioxolo(4,5-g)pyrano(3,4:6,7)indolizino(1,2-b)quinoline-8,11(7H,13H)-dione,7-ethyl-7-hydroxy-,(7S)
10,11-methylenedioxycamptothecin
10,11-methylenedioxy-20(S)-camptothecin
10,11-methlyenedioxycamptothecin