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Rational Development of MAGL Inhibitors

  • Carlotta Granchi
  • Flavio Rizzolio
  • Isabella Caligiuri
  • Marco Macchia
  • Adriano Martinelli
  • Filippo Minutolo
  • Tiziano Tuccinardi
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)

Abstract

Hit identification and hit-to-lead optimization are key steps of the early drug discovery program. Starting from the X-ray crystal structure of the human monoacylglycerol lipase (hMAGL), we herein describe the computational and experimental procedures that we applied for identifying and optimizing a new active inhibitor of this target enzyme. A receptor-based virtual screening method is reported in details, together with enzymatic assays and a first round of hit optimization.

Key words

Hit identification Hit-to-lead optimization Monoacylglycerol lipase inhibitors Virtual screening MAGL 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Carlotta Granchi
    • 1
  • Flavio Rizzolio
    • 2
    • 3
  • Isabella Caligiuri
    • 2
  • Marco Macchia
    • 1
  • Adriano Martinelli
    • 1
  • Filippo Minutolo
    • 1
  • Tiziano Tuccinardi
    • 1
  1. 1.Department of PharmacyUniversity of PisaPisaItaly
  2. 2.Division of Experimental and Clinical Pharmacology, Department of Molecular Biology and Translational ResearchNational Cancer Institute and Center for Molecular Biomedicine, IRCCSPordenoneItaly
  3. 3.Department of Molecular Science and NanosystemsCa’ Foscari Università di VeneziaVenezia-MestreItaly

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