| Identification | Back Directory | [Name]
10,11-methylenedioxycamptothecin | [CAS]
135415-73-5 | [Synonyms]
RPFYDENHBPRCTN-NRFANRHFSA-N
10,11-methylenedioxycamptothecin
(20RS)-10,11-Methylenedioxycamptothecin
10,11-(Methylenedioxy)-20(S)-camptothecin
10,11-(Methylenedioxy)camptothecin(FL118)
(4S)-4-Ethyl-4-hydroxy-8,9-methylenedioxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
(4S)-4-Hydroxy-4-ethyl-8,9-(methylenedioxy)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
(4S)-4-Ethyl-4β-hydroxy-8,9-(methylenedioxy)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
(4S)-4α-Ethyl-4-hydroxy-8,9-(methylenedioxy)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
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)-
(4S)-4α-Ethyl-4-hydroxy-4,12-dihydro-8,9-methylenedioxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione | [Molecular Formula]
C21H16N2O6 | [MDL Number]
MFCD29078463 | [MOL File]
135415-73-5.mol | [Molecular Weight]
392.36 |
| Chemical Properties | Back Directory | [Boiling point ]
812.1±65.0 °C(Predicted) | [density ]
1?+-.0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
11.18±0.20(Predicted) | [color ]
Light brown to brown | [InChI]
InChI=1S/C21H16N2O6/c1-2-21(26)13-5-15-18-11(7-23(15)19(24)12(13)8-27-20(21)25)3-10-4-16-17(29-9-28-16)6-14(10)22-18/h3-6,26H,2,7-9H2,1H3/t21-/m0/s1 | [InChIKey]
RPFYDENHBPRCTN-NRFANRHFSA-N | [SMILES]
N1C2C(=CC3OCOC=3C=2)C=C2CN3C(C=12)=CC1[C@](CC)(O)C(=O)OCC=1C3=O |
| Hazard Information | Back Directory | [Uses]
FL118 (10,11-(Methylenedioxy)-20(S)-camptothecin), a Camptothecin.html" class="link-product" target="_blank">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 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 | | 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 |
| 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. |
| [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. DOI:10.1002/ctm2.881
[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. DOI:10.1039/c9ra00315k
[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. PMID:26692923 |
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