Strategies Employed for the Development of PARP Inhibitors.
Methods Mol Biol
; 1608: 271-297, 2017.
Article
in En
| MEDLINE
| ID: mdl-28695516
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enzyme Inhibitors
/
Poly(ADP-ribose) Polymerase Inhibitors
/
Poly (ADP-Ribose) Polymerase-1
Limits:
Animals
/
Humans
Language:
En
Journal:
Methods Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2017
Document type:
Article
Affiliation country:
United States