Elomotecan TFA
Elomotecan TFA (BN 80927 TFA) is an orally active, potent inhibitor of topoisomerases I and II and a homocamptothecin (hCPT) analogue. Elomotecan TFA possesses a dual inhibitory mechanism: it acts as a topoisomerase I poison by stabilizing the DNA-enzyme complex while simultaneously serving as a catalytic inhibitor of topoisomerase II. Elomotecan TFA is used in research concerning various advanced and multidrug-resistant (MDR) solid tumors (such as prostate, colon, and breast cancers).
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- Formule: C31H33ClF3N3O6
- Masse moléculaire:636.06
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
Description
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Topoisomerase I |
Topoisomerase II |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HT-29 | IC50 |
21 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| DU-145 | IC50 |
3 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| PC-3 | IC50 |
81 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| SK-OV-3 | IC50 |
13 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| A549 | IC50 |
17 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| MCF7 | IC50 |
48 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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15256467 |
| MCF7 | IC50 |
48 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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15256467 |
| T-24 | IC50 |
2.2 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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15256467 |
| K562 | IC50 |
8.4 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| HL-60 | IC50 |
7.4 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
15256467 |
| K562/Adr | IC50 |
18 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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15256467 |
| HT-29 | IC50 |
21 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
11193907 |
| DU-145 | IC50 |
3.13 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
11193907 |
| HL-60 | IC50 |
7.4 nM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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11193907 |
In Vitro
Elomotecan (BN 80927) (1-10 μM; 60 min) TFA promotes and stabilizes the accumulation of Topo I-DNA cleavable complexes in live HT29 cells[1].
Elomotecan (0.02-50 μM; 1 h) TFA rapidly induces and highly stabilizes DNA-protein complexes (DPCs) in HT29 cells[1].
Elomotecan (5.12 × 10-13 to 1 × 10-6 M; 72 h) TFA exhibits potent antiproliferative activity against various human tumor cell lines (including HT29 (IC50 = 21 nM), DU145 (IC50 = 3 nM), PC3 (IC50 = 81 nM), SKOV3 (IC50 = 13 nM), A549 (IC50 = 17 nM), MCF7 (IC50 = 48 nM), T24 (IC50 = 2.2 nM), K562 (IC50 = 8.4 nM), HL60 (IC50 = 7.4 nM)) and drug-resistant strains expressing MDR pumps (T24anp (IC50 = 2.9 nM), K562adr (IC50 = 18 nM), HL60adr (IC50 = 1.3 nM), HL60dnr (IC50 = 32 nM)) or Topo I mutations (KB-STP2 (IC50 = 230 nM))[1].
Elomotecan (0.64-400 nM; 16 h) TFA exerts cytotoxic effects on cell survival in HT29 cells synchronized in the quiescent G0-G1 phase[1].
Elomotecan (72 h) TFA potently inhibits cell proliferation in human tumor cell lines (HT29 (IC50 = 21 nM), DU145 (IC50 = 3.13 nM), HL60 (IC50 = 7.4 nM)) and their drug-resistant strains[3].
Elomotecan (0.64-400 nM; 3-day culture following brief exposure) TFA in synchronized quiescent G0/G1 HT29 It exhibits potent cytotoxic effects in cells[3].
Elomotecan (3 h) TFA maintains high stability of the lactone ring in human plasma systems[4].
Elomotecan (1 h) TFA induces the formation of substantial, largely irreversible DNA-protein complexes (DPCs) in HT29 cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:G0-G1 synchronized HT29 cells
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Concentration:0.64, 3.2, 16, 80, 400 nM
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Incubation Time:16 h (followed by 72 h culture in drug-free medium)
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Result:Reduced the survival rate of the synchronized resting cells in a concentration-dependent manner.
In Vivo
Elomotecan (p.o.) TFA exhibits potent antitumor activity, inducing tumor regression in mouse models of human prostate tumor (PC3 and DU145) xenografts[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCr nu/nu athymic nude mice (female, 4-6 week-old) were subcutaneously injected of 5 × 106 human androgen-independent prostate adenocarcinoma cells (PC3 or DU145) into the left dorsal surface[1]
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Dosage:5 mg/kg, 8 mg/kg, 40 mg/kg
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Administration:p.o.; four schedules: once daily for 14 days, twice daily for 14 days, once a week for 3 weeks, and 4-days-on/3-days-off for 3 cycles; mice were monitored until day 50 post-injection
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Result:Significantly reduced the tumor growth rate across multiple schedules.
Increased the mean day of survival (MDS) by up to 175% compared with matched control mice in the preferred twice-a-day schedule.
Produced no toxic deaths, and body weight loss never exceeded 10% during the treatment.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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Masse moléculaire 636.06
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Formule C31H33ClF3N3O6
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SMILES
O=C(OC1)C[C@](O)(CC)C2=C1C(N3CC4=C(CN5CCC(C)CC5)C6=CC(C)=C(Cl)C=C6N=C4C3=C2)=O.OC(C(F)(F)F)=O
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Synonyms
BN 80927 TFA
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Demarquay D, et al. BN80927: a novel homocamptothecin that inhibits proliferation of human tumor cells in vitro and in vivo. Cancer Res. 2004 Jul 15;64(14):4942-9. [Content Brief]
[2]. Trocóniz IF, et al. Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012 Aug;70(2):239-50. [Content Brief]
[3]. Huchet M, et al. The dual topoisomerase inhibitor, BN 80927, is highly potent against cell proliferation and tumor growth. Ann N Y Acad Sci. 2000;922:303-5. [Content Brief]
[4]. Demarquay D, et al. The homocamptothecin, BN 80927, is a potent topoisomerase I poison and topoisomerase II catalytic inhibitor. Ann N Y Acad Sci. 2000;922:301-2. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Elomotecan TFA Related Classifications
HY-13622B Related Classifications
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