PMID- 26588187
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20161126
IS  - 1029-046X (Electronic)
IS  - 1026-776X (Linking)
VI  - 26
IP  - 11
DP  - 2015
TI  - Design of selective TACE inhibitors using molecular docking studies: Synthesis 
      and preliminary evaluation of anti-inflammatory and TACE inhibitory activity.
PG  - 905-23
LID - 10.1080/1062936X.2015.1095240 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) has been considered one 
      of the principal therapeutic targets for the treatment of TNF-dependent 
      pathologies. Several TACE inhibitors have been reported, but none of them has 
      been successfully passed to phase II clinical trials. In the present work, we 
      attempted to design highly selective new non-hydroxamate sulfonamide TACE 
      inhibitors. The docking study was performed on one of the crystal structures of 
      TACE, selected based on its resolution and R value, to tackle the flexibility 
      issue of the active site. The results allowed us to distinguish the analogues 
      with a higher binding affinity toward the active site of TACE and to identify the 
      substituent of analogues needed for binding with the surrounding site of the 
      enzyme. Finally the analogues were docked on crystal structures of six different 
      matrix metalloproteinases (MMPs) for a selectivity study of TACE over MMPs. Some 
      of these analogues were synthesized and subjected to preliminary testing for in 
      vivo anti-inflammatory activity and TACE inhibitory activity.
FAU - Sarkate, A P
AU  - Sarkate AP
AD  - a Department of Pharmaceutical Chemistry , Sinhgad Institute of Pharmacy , Pune , 
      Maharashtra , India.
FAU - Murumkar, P R
AU  - Murumkar PR
AD  - a Department of Pharmaceutical Chemistry , Sinhgad Institute of Pharmacy , Pune , 
      Maharashtra , India.
FAU - Lokwani, D K
AU  - Lokwani DK
AD  - b Department of Chemical Technology , Dr. Babasaheb Ambedkar Marathwada 
      University , Aurangabad , Maharashtra , India.
FAU - Kandhare, A D
AU  - Kandhare AD
AD  - c Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth 
      Deemed University , Pune , Maharashtra , India.
FAU - Bodhankar, S L
AU  - Bodhankar SL
AD  - c Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth 
      Deemed University , Pune , Maharashtra , India.
FAU - Shinde, D B
AU  - Shinde DB
AD  - b Department of Chemical Technology , Dr. Babasaheb Ambedkar Marathwada 
      University , Aurangabad , Maharashtra , India.
FAU - Bothara, K G
AU  - Bothara KG
AD  - a Department of Pharmaceutical Chemistry , Sinhgad Institute of Pharmacy , Pune , 
      Maharashtra , India.
LA  - eng
PT  - Journal Article
PL  - England
TA  - SAR QSAR Environ Res
JT  - SAR and QSAR in environmental research
JID - 9440156
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9000-07-1 (Carrageenan)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, rat)
SB  - IM
MH  - ADAM Proteins/*antagonists & inhibitors/*chemistry
MH  - ADAM17 Protein
MH  - Animals
MH  - Anti-Inflammatory Agents/*chemistry/pharmacology
MH  - Carrageenan
MH  - Catalytic Domain
MH  - Drug Design
MH  - Edema/chemically induced/drug therapy
MH  - Female
MH  - Male
MH  - Matrix Metalloproteinases/chemistry
MH  - *Molecular Docking Simulation
MH  - Quantitative Structure-Activity Relationship
MH  - Rats
MH  - Sulfonamides/*chemistry/pharmacology
MH  - Tumor Necrosis Factor-alpha/blood
OTO - NOTNLM
OT  - MMPs
OT  - TACE
OT  - glide
OT  - induced fit docking (IFD)
OT  - sulfonamide
EDAT- 2015/11/21 06:00
MHDA- 2016/08/02 06:00
CRDT- 2015/11/21 06:00
PHST- 2015/11/21 06:00 [entrez]
PHST- 2015/11/21 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
AID - 10.1080/1062936X.2015.1095240 [doi]
PST - ppublish
SO  - SAR QSAR Environ Res. 2015;26(11):905-23. doi: 10.1080/1062936X.2015.1095240.