PMID- 20393763
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20211020
IS  - 0948-5023 (Electronic)
IS  - 0948-5023 (Linking)
VI  - 17
IP  - 1
DP  - 2011 Jan
TI  - Ligand-based and structure-based approaches in identifying ideal pharmacophore 
      against c-Jun N-terminal kinase-3.
PG  - 151-63
LID - 10.1007/s00894-010-0701-0 [doi]
AB  - Structure and ligand based pharmacophore modeling and docking studies carried out 
      using diversified set of c-Jun N-terminal kinase-3 (JNK3) inhibitors are 
      presented in this paper. Ligand based pharmacophore model (LBPM) was developed 
      for 106 inhibitors of JNK3 using a training set of 21 compounds to reveal 
      structural and chemical features necessary for these molecules to inhibit JNK3. 
      Hypo1 consisted of two hydrogen bond acceptors (HBA), one hydrogen bond donor 
      (HBD), and a hydrophobic (HY) feature with a correlation coefficient (r(2)) of 
      0.950. This pharmacophore model was validated using test set containing 85 
      inhibitors and had a good r(2) of 0.846. All the molecules were docked using Glide 
      software and interestingly, all the docked conformations showed hydrogen bond 
      interactions with important hinge region amino acids (Gln155 and Met149)and these 
      interactions were compared with Hypo1 features. The results of ligand based 
      pharmacophore model (LBPM)and docking studies are validated each other. The 
      structure based pharmacophore model (SBPM) studies have identified additional 
      features, two hydrogen bond donors and one hydrogen bond acceptor. The 
      combination of these methodologies is useful in designing ideal pharmacophore 
      which provides a powerful tool for the discovery of novel and selective JNK3 
      inhibitors.
FAU - Kumar, B V S Suneel
AU  - Kumar BV
AD  - bioCampus, GVK Biosciences Private Limited, S-1, Phase-1, TIE, Balanagar, 
      Hyderabad 500037, India.
FAU - Kotla, Rohith
AU  - Kotla R
FAU - Buddiga, Revanth
AU  - Buddiga R
FAU - Roy, Jyoti
AU  - Roy J
FAU - Singh, Sardar Shamshair
AU  - Singh SS
FAU - Gundla, Rambabu
AU  - Gundla R
FAU - Ravikumar, Muttineni
AU  - Ravikumar M
FAU - Sarma, Jagarlapudi A R P
AU  - Sarma JA
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - J Mol Model
JT  - Journal of molecular modeling
JID - 9806569
RN  - 0 (Ligands)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.- (Mitogen-Activated Protein Kinase 10)
SB  - IM
MH  - Catalytic Domain
MH  - Drug Design
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Inhibitory Concentration 50
MH  - Ligands
MH  - Mitogen-Activated Protein Kinase 10/*antagonists & inhibitors/chemistry
MH  - *Models, Molecular
MH  - Protein Binding
MH  - Protein Kinase Inhibitors/*chemistry/metabolism
MH  - *Quantitative Structure-Activity Relationship
MH  - Software
EDAT- 2010/04/16 06:00
MHDA- 2011/12/20 06:00
CRDT- 2010/04/16 06:00
PHST- 2009/09/02 00:00 [received]
PHST- 2010/02/28 00:00 [accepted]
PHST- 2010/04/16 06:00 [entrez]
PHST- 2010/04/16 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
AID - 10.1007/s00894-010-0701-0 [doi]
PST - ppublish
SO  - J Mol Model. 2011 Jan;17(1):151-63. doi: 10.1007/s00894-010-0701-0.