PMID- 23231541
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20161125
IS  - 1746-045X (Electronic)
IS  - 1746-0441 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Feb
TI  - Novel methods and strategies in the discovery of TACE inhibitors.
PG  - 157-81
LID - 10.1517/17460441.2013.744745 [doi]
AB  - INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) is a key player in inflammation and 
      joint damage in rheumatoid arthritis (RA). One treatment approach to exclude 
      TNF-alpha from the biological system is by inhibiting tumor necrosis factor-alpha 
      converting enzyme (TACE), the enzyme responsible for the production of its active 
      form. To date, a number of TACE inhibitors have been reported in the literature 
      from various strategies and methods. AREAS COVERED: The following article 
      presents the design and development strategies for the discovery of novel TACE 
      inhibitors which could be of therapeutic utility for the alleviation of 
      inflammatory conditions. The review is based on literature of the subject from 
      2005 onward. EXPERT OPINION: Discovery of a selective TACE inhibitor has remained 
      a major goal for many academic and pharmaceutical industrial research 
      laboratories for quite some time. Identification of selective TACE inhibitors has 
      proved elusive until recently due to structural similarities between TACE and 
      MMPs. The differences in the shape and size of the S1' pocket of TACE and MMPs 
      could be exploited to design selective TACE inhibitors devoid of any MMP 
      inhibitory activity in the near future. It would be a Herculean task to develop a 
      specific TACE inhibitor for clinical treatment of RA because binding subsites of 
      TACE and MMPs are quite similar. However, developments taking place currently in 
      the field as well as in the application of molecular modeling techniques at a 
      wider scale could yet provide clinically useful selective TACE inhibitors in the 
      not too distant future.
FAU - Murumkar, Prashant R
AU  - Murumkar PR
AD  - The M.S. University of Baroda, Faculty of Technology & Engineering, Pharmacy 
      Department, Kalabhavan, Vadodara-390 001, India.
FAU - Giridhar, Rajani
AU  - Giridhar R
FAU - Yadav, Mange Ram
AU  - Yadav MR
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20121212
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM Proteins/*antagonists & inhibitors
MH  - ADAM17 Protein
MH  - *Drug Design
MH  - Enzyme Inhibitors/*pharmacology
MH  - Humans
MH  - Models, Molecular
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2012/12/13 06:00
MHDA- 2013/07/03 06:00
CRDT- 2012/12/13 06:00
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
AID - 10.1517/17460441.2013.744745 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2013 Feb;8(2):157-81. doi: 10.1517/17460441.2013.744745. 
      Epub 2012 Dec 12.