ABT-888, an Orally Active Poly(ADP-Ribose) Polymerase Inhibitor that Potentiates DNA-Damaging Agents in Preclinical Tumor Models

@article{Donawho2007ABT888AO,
  title={ABT-888, an Orally Active Poly(ADP-Ribose) Polymerase Inhibitor that Potentiates DNA-Damaging Agents in Preclinical Tumor Models},
  author={Cherrie K. Donawho and Yan Luo and Yanping Luo and Thomas D Penning and Joy L. Bauch and Jennifer J. Bouska and Velitchka Bontcheva-Diaz and Bryan F. Cox and Theodore DeWeese and Larry E. Dillehay and Debra C. Ferguson and Nayereh S. Ghoreishi-Haack and David R. Grimm and Ran Guan and Edward Kyu-ho Han and Rhonda R. Holley-Shanks and Boris Hristov and Kenneth B. Idler and Kenneth P. Jarvis and Eric F. Johnson and Lawrence R Kleinberg and Vered Klinghofer and Loren M. Lasko and Xuesong Mike Liu and Kennan Marsh and Thomas Mcgonigal and Jonathan A. Meulbroek and Amanda M. Olson and Joann P. Palma and Luis E. Rodriguez and Yan Shi and Jason A. Stavropoulos and Alan C. Tsurutani and Gui-dong Zhu and Saul H. Rosenberg and Vincent L. Giranda and David J. Frost},
  journal={Clinical Cancer Research},
  year={2007},
  volume={13},
  pages={2728 - 2737}
}
Purpose: To evaluate the preclinical pharmacokinetics and antitumor efficacy of a novel orally bioavailable poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888. Experimental Design:In vitro potency was determined in a PARP-1 and PARP-2 enzyme assay. In vivo efficacy was evaluated in syngeneic and xenograft models in combination with temozolomide, platinums, cyclophosphamide, and ionizing radiation. Results: ABT-888 is a potent inhibitor of both PARP-1 and PARP-2 with Kis of 5.2 and 2.9 nmol/L… 

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