posted on 2023-05-24, 14:20authored byShaun D. Fontaine, Christopher W. Carreras, Ralph R. Reid, Gary W. Ashley, Daniel V. Santi
Treatment of MX-1 xenografts (N-6/group) with single doses of PEG-Exa 3A and PLX038A. A, Median relative tumor volume ± interquartile range versus t. The starting tumor volume for all groups was 129 ± 38 mm3. P values at 21 days from one-way ANOVA analysis versus vehicle were: 0.008 (PLX038A), 0.01 (2.5 μmol/kg PEG-Exa), 0.0002 (5 μmol/kg PEG-Exa), <0.0001 (10 and 15 μmol/kg PEG-Exa). B, Median relative body weight of mice over time. Mice (N = 6 per group) received a single intraperitoneal dose of vehicle (●), PEG-Exa at 15 μmol/kg (■), 10 μmol/kg (▲), 5 μmol/kg (▼), 2.5 μmol/kg (◆), or PLX038A at 15 μmol/kg (○).
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ARTICLE ABSTRACT
A circulating conjugate that slowly releases Exa is described. It is efficacious after a single dose and synergistic with ATR and PARP inhibitors.