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The Discovery and Development of HCV NS3 Protease Inhibitor Paritaprevir

  • Keith F. McDanielEmail author
  • Yi-Yin Ku
  • Ying Sun
  • Hui-Ju Chen
  • Jason Shanley
  • Timothy Middleton
  • Yat Sun Or
  • Dale Kempf
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 31)

Abstract

Hepatitis C virus (HCV) NS3/4A protease inhibitors play an important role in several of the combination regimens that have revolutionized the treatment of this disease, offering patients an excellent chance for a complete cure. Starting from inhibitors incorporating oxime-based P*-shelf moieties, a collaborative effort between Abbott Laboratories and Enanta Pharmaceuticals generated ABT-450 (paritaprevir, a component of Technivie™ and Viekira Pak™), incorporating novel P*-phenanthridine and P3-amide capping groups and pharmacokinetically boosted by ritonavir. The discovery and development of ABT-450 enabled one of the first IFN-free combination therapies for HCV genotype 1 infection and contributed to the transformation of the treatment of this chronic and deadly disease.

Keywords

AbbVie ABT-450 Enanta Hepatitis C virus (HCV) Macrocycle Paritaprevir Phenanthridine Protease inhibitor Ritonavir 

Notes

Acknowledgments

The authors would like to acknowledge the assistance of Tami Pilot-Matias (virology discussions), Charles Hutchins (molecular modeling support), and Lisa Hasvold (proofreading) in the preparation of this manuscript.

Compliance with Ethical Standards

Funding The study was supported by AbbVie.

Conflict of Interest

K.F.M., Y.-Y.K, H.-J.C., J.S., T.M., and D.K. are current AbbVie employees and may hold AbbVie stock or options. Y.S. and Y.S.O. are current or former Enanta employees and may hold Enanta stock or options. The design and study conduct for this research were provided by AbbVie and Enanta. AbbVie and Enanta participated in the interpretation of the data and review and approval of the publication.

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

The authors would like to thank the patients and their families as well as study site staff who participated in the clinical trials of paritaprevir.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Keith F. McDaniel
    • 1
    Email author
  • Yi-Yin Ku
    • 1
  • Ying Sun
    • 2
  • Hui-Ju Chen
    • 1
  • Jason Shanley
    • 1
  • Timothy Middleton
    • 1
  • Yat Sun Or
    • 2
  • Dale Kempf
    • 1
  1. 1.AbbVie, Inc.North ChicagoUSA
  2. 2.Enanta PharmaceuticalsWatertownUSA

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