Strategies employed for the development of PARP inhibitors
This chapter describes the approaches taken in the development of the first PARP inhibitor to enter into clinical trial, AG-014699. We describe the general principles of crystal-based drug design, the purification, and crystallization of the PARP-1 catalytic domain, and how this approach was used to develop highly potent PARP inhibitors based on the nicotinamide pharmacophore. Several methods have been used to determine the inhibitory potency of designed inhibitors in cell-free and whole cell assays; each is described with reference to its advantages and disadvantages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:780 |
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| Enthalten in: |
Methods in molecular biology (Clifton, N.J.) - 780(2011) vom: 14., Seite 463-89 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Canan, Stacie [VerfasserIn] |
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| Links: |
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| Themen: |
Enzyme Inhibitors |
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| Anmerkungen: |
Date Completed 05.01.2012 Date Revised 19.11.2015 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/978-1-61779-270-0_28 |
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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 into clinical trial, AG-014699. We describe the general principles of crystal-based drug design, the purification, and crystallization of the PARP-1 catalytic domain, and how this approach was used to develop highly potent PARP inhibitors based on the nicotinamide pharmacophore. Several methods have been used to determine the inhibitory potency of designed inhibitors in cell-free and whole cell assays; each is described with reference to its advantages and disadvantages | ||
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| 700 | 1 | |a Curtin, Nicola |e verfasserin |4 aut | |
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