diflomotecan: a fluorinated E-ring modified camptothecin; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
diflomotecan : An organic heteropentacyclic compound that is (5R)-8-[(6,7-difluoroquinolin-3-yl)methyl]-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione in which position 7 of the oxepinopyridine moiety is joined to position 3 of the difluoroquinoine ring by a single bond. An E-ring modified camptothecin analogue that has greater lactone stability in plasma compared with other topoisomerase I inhibitors. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 219023 |
| CHEMBL ID | 306280 |
| CHEBI ID | 144046 |
| SCHEMBL ID | 1650167 |
| MeSH ID | M0511672 |
| Synonym |
|---|
| CHEMBL306280 |
| unii-qkt1lc4j1p |
| 3h,15h-oxepino(3',4':6,7)indolizino(1,2-b)quinoline-3,15-dione, 5-ethyl-9,10-difluoro-1,4,5,13-tetrahydro-5-hydroxy-, (5r)- |
| qkt1lc4j1p , |
| diflomotecan [inn] |
| bn 80915 |
| diflomotecanum |
| CHEBI:144046 |
| 220997-97-7 |
| (5r)-5-ethyl-9,10-difluoro-5-hydroxy-1,4,5,13-tetrahydro-3h,15h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione |
| bn80915 |
| diflomotecan |
| (5r)-5-ethyl-9,10-difluoro-1,4,5,13-tetrahydro-5-hydroxy-3h,15h-oxepino(3',4':6,7)indolizino(1,2-b)quinoline-3,15-dione |
| bn-80915 |
| 3h,15h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione,5-ethyl-9,10-difluoro-1,4,5,13-tetrahydro-5-hydroxy-, (5r)- |
| diflomotecan [who-dd] |
| SCHEMBL1650167 |
| (5r)-5-ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h -oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione |
| LFQCJSBXBZRMTN-OAQYLSRUSA-N |
| (5r)-5-ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione |
| (5r)-5-ethyl-9,1 0-difluoro-5-hydroxy-4,5,13,1 5-tetrahydro-1h,3h-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione |
| (20r)-20-ethyl-6,7-difluoro-20-hydroxy-17-oxa-3,13-diazapentacyclo[11.9.0.02,11.04,9.015,21]docosa-1(22),2(11),3,5,7,9,15(21)-heptaene-14,18-dione |
| Q27287310 |
| (r)-5-ethyl-9,10-difluoro-5-hydroxy-4,5-dihydrooxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15(1h,13h)-dione |
| DTXSID201026358 |
| CS-0007467 |
| HY-13611 |
| AKOS040757407 |
Diflomotecan is an E-ring modified camptothecin analogue. It possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. " | ( Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors. de Jonge, MJ; Devlin, M; Gelderblom, H; Obach, R; Pentheroudakis, G; Principe, P; Pruñonosa, J; Salazar, R; Seguy, F; Twelves, C; van Hooije, C; Verweij, J, 2003) | 2.01 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure." | ( Diflomotecan, a promising homocamptothecin for cancer therapy. Gelderblom, H; Kroep, JR, 2009) | 2.52 |
| "Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure." | ( Diflomotecan, a promising homocamptothecin for cancer therapy. Gelderblom, H; Kroep, JR, 2009) | 2.52 |
Diflomotecan administered as a 20-min intravenous infusion 3-weekly is characterised by a variable pharmacokinetic profile. Pharmacokinetic analyses revealed a less than dose-proportional increase in diflombecan and for the two metabolites BN80942 and P-20.
Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated.
The current work integrates cell-cycle dynamics occurring in the bone marrow compartment as a key element in the structure of a semimechanistic pharmacokinetic/pharmacodynamic model for neutropenic effects. Alternative oral dosing schedules of diflomotecan have been shown to display a more predictable PK/PD and safety profile.
| Excerpt | Relevance | Reference |
|---|---|---|
| " Cohorts of six patients were recruited sequentially to one of three fixed starting dose groups-2, 4, or 7 mg, with drug administered by fixed-dose rather than dosing by body surface area." | ( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009) | 0.6 |
| " Alternative oral dosing schedules of diflomotecan have been shown to display a more predictable PK/PD and safety profile and should be selected for further evaluation in Phase II clinical trials." | ( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009) | 0.87 |
| "The current work integrates cell-cycle dynamics occurring in the bone marrow compartment as a key element in the structure of a semimechanistic pharmacokinetic/pharmacodynamic model for neutropenic effects, aiming to describe, with the same set of system- and drug-related parameters, longitudinal data of neutropenia gathered after the administration of the anticancer drug diflomotecan (9,10-difluoro-homocamptothecin) under different dosing schedules to patients (n = 111) with advanced solid tumors." | ( Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of chemotherapy-induced neutropenic effects of diflomotecan under different dosing schedules. Buil-Bruna, N; Garrido, MJ; Mangas-Sanjuan, V; Soto, E; Trocóniz, IF, 2015) | 0.79 |
| Role | Description |
|---|---|
| EC 5.99.1.2 (DNA topoisomerase) inhibitor | A topoisomerase inhibitor that inhibits the bacterial enzymes of the DNA topoisomerases, Type I class (EC 5.99.1.2) that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. These bacterial enzymes reduce the topological stress in the DNA structure by relaxing negatively, but not positively, supercoiled DNA. |
| antineoplastic agent | A substance that inhibits or prevents the proliferation of neoplasms. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| organic heteropentacyclic compound | |
| organofluorine compound | An organofluorine compound is a compound containing at least one carbon-fluorine bond. |
| tertiary alcohol | A tertiary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has three other carbon atoms attached to it. |
| epsilon-lactone | Any lactone with a seven-membered ring. |
| organonitrogen heterocyclic compound | Any organonitrogen compound containing a cyclic component with nitrogen and at least one other element as ring member atoms. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID56882 | Stimulation of pKMp27 DNA cleavage by human DNA topoisomerase I in presence of 0.1 uM of compound | 2000 | Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11 | Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. |
| AID84438 | Cytotoxicity against HT-29 tumor cell line determined by WST-1 assay | 2000 | Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11 | Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. |
| AID8663 | Cytotoxicity against A549 tumor cell line determined by WST-1 assay | 2000 | Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11 | Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. |
| AID745335 | Cytotoxicity against human A549 cells by WST assay | 2013 | European journal of medicinal chemistry, May, Volume: 63 | Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents. |
| AID208523 | Cytotoxicity against T24 tumor cell line determined by WST-1 assay | 2000 | Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11 | Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. |
| AID745334 | Cytotoxicity against human chemo-resistant T24 cells by WST assay | 2013 | European journal of medicinal chemistry, May, Volume: 63 | Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 14 (82.35) | 29.6817 |
| 2010's | 3 (17.65) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (20.09) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 4 (23.53%) | 5.53% |
| Reviews | 3 (17.65%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 10 (58.82%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||