PMID- 22299579
OWN - NLM
STAT- MEDLINE
DCOM- 20130912
LR  - 20211021
IS  - 1475-6374 (Electronic)
IS  - 1475-6366 (Print)
IS  - 1475-6366 (Linking)
VI  - 28
IP  - 3
DP  - 2013 Jun
TI  - Evaluation of a dithiocarbamate derivative as an inhibitor of human 
      glutaredoxin-1.
PG  - 456-62
LID - 10.3109/14756366.2011.649267 [doi]
AB  - CONTEXT: Glutaredoxins (GRX) are involved in the regulation of thiol redox state. 
      GRX-1 is a cytosolic enzyme responsible for the catalysis of deglutathionylation 
      of proteins. To date, very few inhibitors of GRX-1 have been reported. OBJECTIVE: 
      The objective of this paper is to report 
      2-acetylamino-3-[4-(2-acetylamino-2-carboxyethyl-sulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic 
      acid (2-AAPA) as an inhibitor of human GRX-1. MATERIALS AND METHODS: The 
      mechanism of inhibition of GRX-1 was investigated using dialysis, substrate 
      protection, and mass spectrometry. RESULTS: 2-AAPA inhibits GRX-1 in a time and 
      concentration dependent manner. The activity did not return following dialysis 
      indicating that inhibition is irreversible. Results of substrate protection and 
      mass spectrometry indicate that the inhibition is occurring at the active site. 
      The compound also produced GRX inhibition in human ovarian cancer cells. 
      DISCUSSION: 2-AAPA is an irreversible GRX-1 inhibitor with similar or greater 
      potency compared to previously reported inhibitors. CONCLUSION: The inhibition of 
      GRX-1 by 2-AAPA could be used as a tool to study thiol redox state.
FAU - Sadhu, Satya S
AU  - Sadhu SS
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State 
      University, Brookings, SD, USA.
FAU - Callegari, Eduardo
AU  - Callegari E
FAU - Zhao, Yong
AU  - Zhao Y
FAU - Guan, Xiangming
AU  - Guan X
FAU - Seefeldt, Teresa
AU  - Seefeldt T
LA  - eng
GR  - R15 CA120062/CA/NCI NIH HHS/United States
GR  - CA120062-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120203
PL  - England
TA  - J Enzyme Inhib Med Chem
JT  - Journal of enzyme inhibition and medicinal chemistry
JID - 101150203
RN  - 0 
      (2-acetylamino-3-(4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl)propionic 
      acid)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (GLRX protein, human)
RN  - 0 (Glutaredoxins)
RN  - 0 (Thiocarbamates)
RN  - GAN16C9B8O (Glutathione)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*analogs & derivatives/pharmacology
MH  - Cell Line, Tumor/drug effects
MH  - Dialysis
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Enzyme Inhibitors/*pharmacology
MH  - Glutaredoxins/*antagonists & inhibitors
MH  - Glutathione/metabolism
MH  - Humans
MH  - Thiocarbamates/chemistry/*pharmacology
PMC - PMC4310727
MID - NIHMS657872
COIS- Declaration of Interest Funding for this project was provided by the National 
      Institutes of Health (CA120062-01).
EDAT- 2012/02/04 06:00
MHDA- 2013/09/13 06:00
PMCR- 2015/01/29
CRDT- 2012/02/04 06:00
PHST- 2012/02/04 06:00 [entrez]
PHST- 2012/02/04 06:00 [pubmed]
PHST- 2013/09/13 06:00 [medline]
PHST- 2015/01/29 00:00 [pmc-release]
AID - 10.3109/14756366.2011.649267 [doi]
PST - ppublish
SO  - J Enzyme Inhib Med Chem. 2013 Jun;28(3):456-62. doi: 
      10.3109/14756366.2011.649267. Epub 2012 Feb 3.