Strategies Employed for the Development of PARP Inhibitors
This chapter describes the approaches taken in the development of the first PARP inhibitor to enter clinical trial, rucaparib (now called Rubraca), in 2003. We describe the general principles of crystal-based drug design, the purification and crystallization of the PARP-1 catalytic domain and how this was used to develop highly potent PARP inhibitors, based on the nicotinamide pharmacophore. Several methods have been used to determine the inhibitory potency in cell-free and whole cell assays, each described with reference to its advantages and disadvantages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1608 |
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| Enthalten in: |
Methods in molecular biology (Clifton, N.J.) - 1608(2017) vom: 20., Seite 271-297 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Canan, Stacie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2018 Date Revised 22.06.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/978-1-4939-6993-7_18 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a This chapter describes the approaches taken in the development of the first PARP inhibitor to enter clinical trial, rucaparib (now called Rubraca), in 2003. We describe the general principles of crystal-based drug design, the purification and crystallization of the PARP-1 catalytic domain and how this was used to develop highly potent PARP inhibitors, based on the nicotinamide pharmacophore. Several methods have been used to determine the inhibitory potency in cell-free and whole cell assays, each described with reference to its advantages and disadvantages | ||
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| 700 | 1 | |a Curtin, Nicola J |e verfasserin |4 aut | |
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