PMID- 15864271
OWN - NLM
STAT- MEDLINE
DCOM- 20050603
LR  - 20210109
IS  - 1474-1776 (Print)
IS  - 1474-1776 (Linking)
VI  - 4
IP  - 5
DP  - 2005 May
TI  - Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors.
PG  - 421-40
AB  - Poly(ADP-ribose) polymerases (PARPs) are involved in the regulation of many 
      cellular functions. Three consequences of the activation of PARP1, which is the 
      main isoform of the PARP family, are particularly important for drug development: 
      first, its role in DNA repair; second, its capacity to deplete cellular energetic 
      pools, which culminates in cell dysfunction and necrosis; and third, its capacity 
      to promote the transcription of pro-inflammatory genes. Consequently, 
      pharmacological inhibitors of PARP have the potential to enhance the cytotoxicity 
      of certain DNA-damaging anticancer drugs, reduce parenchymal cell necrosis (for 
      example, in stroke or myocardial infarction) and downregulate multiple 
      simultaneous pathways of inflammation and tissue injury (for example, in 
      circulatory shock, colitis or diabetic complications). The first ultrapotent 
      novel PARP inhibitors have now entered human clinical trials. This article 
      presents an overview of the principal pathophysiological pathways and mechanisms 
      that are governed by PARP, followed by the main structures and therapeutic 
      actions of various classes of novel PARP inhibitors.
FAU - Jagtap, Prakash
AU  - Jagtap P
AD  - Inotek Pharmaceuticals Corp., Suite 419E, 100 Cummings Center, Beverly, 
      Massachusetts 01915, USA.
FAU - Szabo, Csaba
AU  - Szabo C
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Nat Rev Drug Discov
JT  - Nature reviews. Drug discovery
JID - 101124171
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - Animals
MH  - Enzyme Inhibitors/chemistry/pharmacology/*therapeutic use
MH  - Humans
MH  - *Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/metabolism
RF  - 170
EDAT- 2005/05/03 09:00
MHDA- 2005/06/04 09:00
CRDT- 2005/05/03 09:00
PHST- 2005/05/03 09:00 [pubmed]
PHST- 2005/06/04 09:00 [medline]
PHST- 2005/05/03 09:00 [entrez]
AID - nrd1718 [pii]
AID - 10.1038/nrd1718 [doi]
PST - ppublish
SO  - Nat Rev Drug Discov. 2005 May;4(5):421-40. doi: 10.1038/nrd1718.