Journal: PLoS ONE

Article Title: A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy

doi: 10.1371/journal.pone.0054161

Figure Lengend Snippet: Chemical structure of ABT-888 and compound 4a (C 13 H 16 N 4 O, 244.29 g/mol).

Article Snippet: Compound 4a ( ) was provided by Abbott Laboratories (Abbott Laboratories, Abbott Park, IL).

Techniques:

Journal: PLoS ONE

Article Title: A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy

doi: 10.1371/journal.pone.0054161

Figure Lengend Snippet: (A) . Time course of mice mean body weight is shown after i.p. administration of 50 mg/kg compound 4a in combination with platinum drugs, platinum drugs alone, or vehicle. (B) Time course of mean horizontal distance traveled in 20 min is shown after i.p. dosing with 50 mg/kg compound 4a in combination with platinum drugs, platinum drugs alone, or vehicle. Similarly, no effect is observed with 50 mg/kg compound 4a on control mice. Data represent the mean ± S.E.M. of 7–8 mice, two-way ANOVA followed with post hoc analysis.

Article Snippet: Compound 4a ( ) was provided by Abbott Laboratories (Abbott Laboratories, Abbott Park, IL).

Techniques: Control

Journal: PLoS ONE

Article Title: A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy

doi: 10.1371/journal.pone.0054161

Figure Lengend Snippet: (A) After baseline behavioral testing, mice are randomized to experimental groups and PARP inhibitor compound 4a treatment by i.p. injection started two days before and continued with cisplatin or oxaliplatin drug regimen. Behavioral testing were conducted 24 hours after the last 10 th doses at week 3, and at post- chemotherapy or follow up evaluation at weeks 6 and 8. Behavioral assays: VF (VonFrey), RH (Radiant Heat), CP (Cold Plate). (B) Dosing with 50 mg/kg compound 4a or 25 mg/kg compound 4a in combination with cisplatin reversibly reduces mechanical allodynia in cisplatin- induced neuropathy mice compared to cisplatin alone at weeks 3, 6, and 8. Similarly, i.p. dosing with 50 mg/kg compound 4a in combination with oxaliplatin prevents mechanical allodynia in oxaliplatin-induced neuropathy mice compared to oxaliplatin alone at weeks 3 and 6. (C) . Dosing with 50 mg/kg of compound 4a in combination with cisplatin improves thermal hyperalgesia in cisplatin-induced neuropathy mice compared to cisplatin alone at weeks 3, 6, and 8. Similarly, dosing with 25 mg of compound 4a in combination with cisplatin reduces thermal hyperalgesia in cisplatin-induced neuropathy mice compared to cisplatin alone at weeks 6 and 8. Oxaliplatin did not elicit thermal hyperalgesia in mice. (D) . Dosing with 50 mg/kg compound 4a in combination with oxaliplatin reduces oxaliplatin-induced cold hyperalgesia compared to oxaliplatin alone at weeks 3, 6, and 8. Cisplatin did not induce cold hyperalgesia in mice. No effect of compound 4a on control mice. Data represent the mean ± S.E.M. of 7–8 mice, * P <0.05; ** P <0.01; *** P <0.001, two-way ANOVA followed with post hoc analysis.

Article Snippet: Compound 4a ( ) was provided by Abbott Laboratories (Abbott Laboratories, Abbott Park, IL).

Techniques: Injection, Control