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Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program.

ABSTRACT: Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 ?M) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 ?M). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft.

SUBMITTER: Kurmasheva RT

PROVIDER: S-EPMC3951603 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program.

Kurmasheva Raushan T RT Reynolds C Patrick CP Kang Min H MH Allievi Cecilia C Houghton Peter J PJ Smith Malcolm A MA

Pediatric blood & cancer 20131026 5

Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 μM) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 μM). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels ...[more]

PMID: 24166988

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Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program.

Project description:AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP in vivo panels (40 or 60 mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC(50) value of 41 nM and exhibited activity consistent with a cytotoxic effect. In vivo AT13387 induced significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts. No objective tumor responses were observed. In vivo AT13387 demonstrated only modest single agent activity.

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Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program.

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| S-EPMC4248662 | biostudies-literature

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