Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination

Journal of Medicinal Chemistry
Philip JonesCarlo Toniatti

Abstract

Poly(ADP-ribose) polymerases (PARPs) are involved in DNA repair following damage by endogenous or exogenous processes. It has become clear over the past decade that inhibition of PARP in the context of defects in other DNA repair mechanisms provide a tumor specific way to kill cancer cells. We describe the rationale for this approach and the design and discovery of niraparib, a potent PARP-1/2 inhibitor with good cell based activity, selectivity for cancer over normal cells, and oral bioavailability. Niraparib was characterized in a number of preclinical models before moving to phase I clinical trials, where it showed excellent human pharmacokinetics suitable for once a day oral dosing, achieved its pharmacodynamic target for PARP inhibition, and had promising activity in cancer patients. It is currently being tested in phase 3 clinical trials as maintenance therapy in ovarian cancer and as a treatment for breast cancer.

References

Feb 7, 1980·Nature·B W DurkaczS Shall
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·J M de MurciaG de Murcia
Aug 6, 1997·Journal of the National Cancer Institute·R SimonM C Christian
Feb 8, 2002·Cell·Ashok R Venkitaraman
Jul 27, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jean-Christophe AméGilbert de Murcia
Sep 3, 2004·Nature Reviews. Cancer·Steven A Narod, William D Foulkes
Oct 29, 2004·Nature Reviews. Cancer·Nicholas TurnerAlan Ashworth
May 3, 2005·Nature Reviews. Drug Discovery·Prakash Jagtap, Csaba Szabó
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lucio Tentori, Grazia Graziani
Jan 30, 2007·Molecular Cancer Research : MCR·Christiana DelloRussoElizabeth M Swisher
Mar 17, 2007·Molecular Cancer Therapeutics·Huw D ThomasNicola J Curtin
Sep 28, 2007·Anti-cancer Agents in Medicinal Chemistry·Tomasz Zaremba, Nicola Jane Curtin
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Paul O Hassa, Michael O Hottiger
Oct 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sven RottenbergJos Jonkers
Apr 7, 2010·Journal of Medicinal Chemistry·Dana V Ferraris
Sep 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ruth Plummer
Jan 7, 2011·The New England Journal of Medicine·Joyce O'ShaughnessyCharles Bradley
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jul 23, 2011·Current Drug Targets·Shahneen K SandhuJohann S de Bono
Feb 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anand G PatelScott H Kaufmann
Feb 22, 2012·Nature Biotechnology·Elisabet WahlbergJohan Weigelt
Mar 6, 2012·Nature Structural & Molecular Biology·Arnab Ray ChaudhuriMassimo Lopes
Mar 29, 2012·The New England Journal of Medicine·Jonathan LedermannUrsula Matulonis
Nov 3, 2012·Cancer Research·Junko MuraiYves Pommier
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Feb 6, 2013·Expert Opinion on Therapeutic Patents·Gianluca PapeoAlessandra Cirla
Jul 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuqiao ShenAlan Ashworth
Oct 2, 2013·Nature Reviews. Drug Discovery·Ken Garber
Oct 17, 2013·Nature Reviews. Clinical Oncology·Joaquin MateoJohann S de Bono
Oct 30, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S De SummaS Tommasi
Nov 15, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J-M LeeE C Kohn
Nov 16, 2013·Science·Sebastian M B Nijman, Stephen H Friend

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Citations

Jun 18, 2016·Journal of Biomolecular Structure & Dynamics·Ramin Ekhteiari SalmasSerdar Durdagi
Oct 1, 2016·Nuclear Medicine and Biology·Redmond-Craig AndersonRobert H Mach
Sep 2, 2016·Biochemistry·Safnas F AbdulSalamEdward J Merino
Nov 2, 2016·Journal of Medicinal Chemistry·Valentina NiedduGabriele Murineddu
May 17, 2018·Anais Da Academia Brasileira De Ciências·Luma G MagalhaesAdriano D Andricopulo
Apr 6, 2018·Expert Opinion on Drug Metabolism & Toxicology·Teresa C Longoria, Krishnansu S Tewari
May 28, 2016·Gynecologic Oncology Research and Practice·Robert S Meehan, Alice P Chen
Jun 2, 2018·Future Oncology·Josee-Lyne EthierAmit M Oza
Dec 13, 2018·Chemical Communications : Chem Comm·Qiuye ZhaoYu Rao
Jan 24, 2019·Journal of Cellular and Molecular Medicine·Xuan JiangZhenyu Zhang
Apr 3, 2019·Journal of Clinical Medicine·Man Yee T KeungJaydutt V Vadgama
Feb 10, 2018·Current Medicinal Chemistry·Monika TomaTomasz Sliwinski
Sep 29, 2019·Cancer Medicine·Ashwin ChandraRiyaz Basha
Oct 28, 2019·Investigational New Drugs·Stergios BoussiosNicholas Pavlidis
Mar 17, 2020·The Annals of Pharmacotherapy·Lloreta KerliuEvan R Horton
Aug 12, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Zhimin ZhangZhengrong Shen
Nov 12, 2015·Frontiers in Oncology·Stefan Symeonides, Charlie Gourley
Nov 26, 2016·Journal of Experimental & Clinical Cancer Research : CR·Aniello CerratoAngela Celetti
Aug 2, 2017·Cancer Chemotherapy and Pharmacology·Gayathri SrinivasanRobert Hromas
May 17, 2017·International Journal of Clinical Oncology·Katsutoshi OdaTomoyuki Fujii
May 26, 2017·Current Treatment Options in Oncology·Praveen Ramakrishnan GeethakumariWm Kevin Kelly
Oct 19, 2019·Targeted Oncology·Esha SachdevMonica M Mita
May 6, 2017·Drugs·Lesley J Scott
Sep 12, 2018·Molecular Cancer Research : MCR·Abid R MattooJ Milburn Jessup
Jun 3, 2020·Blood Reviews·Claire FritzEunice S Wang
Jan 8, 2021·Journal of Experimental & Clinical Cancer Research : CR·Pietro Paolo VitielloErika Martinelli
Mar 17, 2021·Expert Opinion on Investigational Drugs·Luigi Della CorteGiuseppe Bifulco
Apr 28, 2021·European Journal of Medicinal Chemistry·Xiaoxia LiangBo Jing
Jun 7, 2021·Bioorganic & Medicinal Chemistry Letters·Hui ShenQihua Zhu
Dec 31, 2016·Journal of the American Chemical Society·Jiarong ShiYang Li
Mar 12, 2019·Journal of the American Chemical Society·Lik Hang YuenRaphael M Franzini

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