PDBsum entry 2j14

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Transcription PDB id
Protein chains
254 a.a. *
GNI ×2
Waters ×129
* Residue conservation analysis
PDB id:
Name: Transcription
Title: 3,4,5-trisubstituted isoxazoles as novel ppardelta agonists: part2
Structure: Peroxisome proliferator-activated receptor delta. Chain: a, b. Fragment: ligand binding domain, residues 165-441. Synonym: ppar-delta, ppar-beta, nuclear hormone receptor 1, nuc1, nuci, ppardelta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
2.8Å     R-factor:   0.224     R-free:   0.284
Authors: R.Epple,M.Azimioara,R.Russo,Y.Xie,X.Wang,C.Cow,J.Wityak, D.Karanewsky,B.Bursulaya,A.Kreusch,T.Tuntland,A.Gerken, M.Iskandar,E.Saez,H.M.Seidel,S.S.Tian
Key ref: R.Epple et al. (2006). 3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2. Bioorg Med Chem Lett, 16, 5488-5492. PubMed id: 16931011 DOI: 10.1016/j.bmcl.2006.08.052
08-Aug-06     Release date:   06-Sep-06    
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Protein chains
Pfam   ArchSchema ?
Q03181  (PPARD_HUMAN) -  Peroxisome proliferator-activated receptor delta
441 a.a.
254 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  


DOI no: 10.1016/j.bmcl.2006.08.052 Bioorg Med Chem Lett 16:5488-5492 (2006)
PubMed id: 16931011  
3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2.
R.Epple, M.Azimioara, R.Russo, Y.Xie, X.Wang, C.Cow, J.Wityak, D.Karanewsky, B.Bursulaya, A.Kreusch, T.Tuntland, A.Gerken, M.Iskandar, E.Saez, H.Martin Seidel, S.S.Tian.
A series of PPARdelta-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARdelta agonist with good in vivo PK properties in mouse (C(max)=5.1 microM, t(1/2)=3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARdelta is discussed.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19624156 G.J.Yu, S.Iwamoto, L.I.Robins, J.C.Fettinger, T.C.Sparks, B.A.Lorsbach, and M.J.Kurth (2009).
3-(Arylthiomethyl)isoxazole-4,5-dicarboxamides: chemoselective nucleophilic chemistry and insecticidal activity.
  J Agric Food Chem, 57, 7422-7426.  
19622862 T.Oyama, K.Toyota, T.Waku, Y.Hirakawa, N.Nagasawa, J.I.Kasuga, Y.Hashimoto, H.Miyachi, and K.Morikawa (2009).
Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures.
  Acta Crystallogr D Biol Crystallogr, 65, 786-795.
PDB codes: 2znn 2zno 2znp 2znq
18566690 H.Miyachi, and Y.Hashimoto (2008).
Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template.
  PPAR Res, 2008, 689859.  
17532641 J.Kasuga, I.Nakagome, A.Aoyama, K.Sako, M.Ishizawa, M.Ogura, M.Makishima, S.Hirono, Y.Hashimoto, and H.Miyachi (2007).
Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) delta-selective agonists.
  Bioorg Med Chem, 15, 5177-5190.  
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