Phase 1 clinical pharmacology study of F14512, a new polyamine- vectorized anti-cancer drug, in naturally occurring canine lymphoma
نویسندگان
چکیده
Authors’ affiliations: Oncovet Clinical Research, SIRIC ONCOLille, Avenue Paul Langevin, 59650 Villeneuve d’Ascq, France Inserm, UMR-S1172, Jean Pierre Aubert Research Centre, 59000 Lille, France Université de Lille, 59000 Lille, France Institut de Recherche Pierre Fabre, Oncology Pharmacokinetics, 3 avenue Hubert Curien, 31035 Toulouse, France Institut de Recherche Pierre Fabre, Experimental Oncology Research Center, 3 avenue Hubert Curien, 31035 Toulouse, France Institut de Recherche Pierre Fabre, Pharmacokinetics, Bel Air de Campans, 81106 Castres, France UPSP 2011-03-101, Interaction Cellules Environnement, Campus Vétérinaire de VetAgroSup, 1 avenue Bourgelat, 69280 Marcy l'Etoile, France
منابع مشابه
Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma.
PURPOSE F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human...
متن کاملAn optimized polyamine moiety boosts the potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512.
Combined computational-experimental analyses explain and quantify the spermine-vectorized F14512's boosted potency as a topoII poison. We found that an optimized polyamine moiety boosts drug binding to the topoII/DNA cleavage complex, rather than to the DNA alone. These results provide new structural bases and key reference data for designing new human topoII poisons.
متن کاملF14512, a potent antitumor agent targeting topoisomerase II vectored into cancer cells via the polyamine transport system.
The polyamine transport system (PTS) is an energy-dependent machinery frequently overactivated in cancer cells with a high demand for polyamines. We have exploited the PTS to selectively deliver a polyamine-containing drug to cancer cells. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine tail support...
متن کاملAn Integrated Drosophila Model System Reveals Unique Properties for F14512, a Novel Polyamine-Containing Anticancer Drug That Targets Topoisomerase II
F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II). The antitumor activity of F14512 in human tumor models is significantly higher than that of oth...
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Canine ehrlichiosis has emerged as one of the most clinically important tick-borne diseases affecting dogs. Eighty-five naturally infected dogs have been investigated, the most consistent clinical signs recorded were fever, emaciation and lymphoadenopathy, anemia, monocytosis, thrompocytopenia, hypoalbuminemia, elevation in liver enzymes and total bilirubin were the most remarkable changes asso...
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