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

Clinical Cancer Research · 2007 · Vol. 13(9) · pp. 2728–2737

Cherrie K. Donawho✉(Abbott Fund)Yan Luo(Abbott Fund)Yanping Luo(Abbott Fund)Thomas D. Penning(Abbott Fund)Joy Bauch(Abbott Fund)Jennifer J. Bouska(Abbott Fund)Velitchka Bontcheva-Diaz(Abbott Fund)Bryan F. Cox(Abbott Fund)Theodore L. DeWeese(Johns Hopkins Medicine)Larry E. Dillehay(Johns Hopkins University)Debra C. Ferguson(Abbott Fund)Nayereh Ghoreishi‐Haack(Abbott Fund)David R. Grimm(Abbott Fund)Ran Guan(Abbott Fund)Edward K. Han(Abbott Fund)Rhonda R. Holley-Shanks(Abbott Fund)Boris Hristov(Johns Hopkins University)Kenneth B. Idler(Abbott Fund)Ken Jarvis(Abbott Fund)Eric F. Johnson(Abbott Fund)Lawrence Kleinberg(Johns Hopkins Medicine)Vered Klinghofer(Abbott Fund)Loren Lasko(Abbott Fund)Xuesong Liu(Abbott Fund)Kennan C. Marsh(Abbott Fund)Thomas McGonigal(Abbott Fund)Jonathan A. Meulbroek(Abbott Fund)Amanda M. Olson(Abbott Fund)Joann P. Palma(Abbott Fund)Luis E. Rodrı́guez(Abbott Fund)Yan Shi(Abbott Fund)Jason Stavropoulos(Abbott Fund)Alan C. Tsurutani(Abbott Fund)Gui‐Dong Zhu(Abbott Fund)Saul H. Rosenberg(Abbott Fund)Vincent L. Giranda(Abbott Fund)David J. Frost(Abbott Fund)

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Abstract

ABT-888 is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. This broad spectrum of chemopotentiation and radiopotentiation makes this compound an attractive candidate for clinical evaluation.

PARP inhibition in cancer therapy DNA Repair Mechanisms Toxin Mechanisms and ImmunotoxinsTemozolomidePARP inhibitorPharmacologyCarboplatinPoly ADP ribose polymeraseMedicineIn vivoCyclophosphamideGliomaBioavailability

MeSH terms

HumansMalePoly(ADP-ribose) Polymerase InhibitorsAdministration, OralAnimalsHaplorhiniBenzimidazolesBiological AvailabilityBlood-Brain BarrierDisease Models, AnimalDNA DamageDogsDrug SynergismEnzyme InhibitorsFemale