PMID- 10377455
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20220408
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 13
DP  - 1999 Jun 22
TI  - Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 
      are associated with human gastrointestinal toxicity: a full in vitro analysis.
PG  - 7563-8
AB  - The beneficial actions of nonsteroid anti-inflammatory drugs (NSAID) can be 
      associated with inhibition of cyclo-oxygenase (COX)-2 whereas their harmful side 
      effects are associated with inhibition of COX-1. Here we report data from two 
      related assay systems, the human whole blood assay and a modified human whole 
      blood assay (using human A549 cells as a source of COX-2). This assay we refer to 
      as the William Harvey Modified Assay. Our aim was to make meaningful comparisons 
      of both classical NSAIDs and newer COX-2-selective compounds. These comparisons 
      of the actions of >40 NSAIDs and novel COX-2-selective agents, including 
      celecoxib, rofecoxib and diisopropyl fluorophosphate, demonstrate a distribution 
      of compound selectivities toward COX-1 that aligns with the risk of serious 
      gastrointestinal complications. In conclusion, this full in vitro analysis of 
      COX-1/2 selectivities in human tissues clearly supports the theory that 
      inhibition of COX-1 underlies the gastrointestinal toxicity of NSAIDs in man.
FAU - Warner, T D
AU  - Warner TD
AD  - The William Harvey Research Institute, St. Bartholomew's and the Royal London 
      School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United 
      Kingdom. t.d.warner@mds.qmw.ac.uk
FAU - Giuliano, F
AU  - Giuliano F
FAU - Vojnovic, I
AU  - Vojnovic I
FAU - Bukasa, A
AU  - Bukasa A
FAU - Mitchell, J A
AU  - Mitchell JA
FAU - Vane, J R
AU  - Vane JR
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS1 protein, human)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
EIN - Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9666
MH  - Anti-Inflammatory Agents, Non-Steroidal/*toxicity
MH  - Cells, Cultured
MH  - Cyclooxygenase 1
MH  - Cyclooxygenase 2
MH  - Digestive System/*drug effects
MH  - Drug Evaluation, Preclinical
MH  - Enzyme Inhibitors/*toxicity
MH  - Humans
MH  - Isoenzymes/*drug effects
MH  - Membrane Proteins
MH  - Prostaglandin-Endoperoxide Synthases/*drug effects
PMC - PMC22126
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
AID - 1466 [pii]
AID - 10.1073/pnas.96.13.7563 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7563-8. doi: 
      10.1073/pnas.96.13.7563.