2J14

3,4,5-Trisubstituted Isoxazoles as Novel PPARdelta Agonists: Part2

Summary for 2J14

• Entry DOI: 10.2210/pdb2j14/pdb
• Related: 1GWX 1Y0S 2AWH 2B50 2BAW 2GWX 3GWX
• Descriptor: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR DELTA, (3-{4-[2-(2,4-DICHLORO-PHENOXY)-ETHYLCARBAMOYL]-5-PHENYL-ISOXAZOL-3-YL}-PHENYL)-ACETIC ACID (3 entities in total)
• Functional Keywords: transcription, nuclear receptor fold, transcription regulation, ppar, zinc, receptor, activator, fatty acids, nuclear protein, alternative splicing, zinc-finger, dna-binding, metal-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: Q03181
• Total number of polymer chains: 2
• Total formula weight: 66384.38

Authors

Epple, R.,Azimioara, M.,Russo, R.,Xie, Y.,Wang, X.,Cow, C.,Wityak, J.,Karanewsky, D.,Bursulaya, B.,Kreusch, A.,Tuntland, T.,Gerken, A.,Iskandar, M.,Saez, E.,Seidel, H.M.,Tian, S.S. (deposition date: 2006-08-08, release date: 2006-09-06, Last modification date: 2023-12-13)

Primary citation

Epple, R.,Azimioara, M.,Russo, R.,Xie, Y.,Wang, X.,Cow, C.,Wityak, J.,Karanewsky, D.,Bursulaya, B.,Kreusch, A.,Tuntland, T.,Gerken, A.,Iskandar, M.,Saez, E.,Seidel, H.M.,Tian, S.S.
3,4,5-Trisubstituted Isoxazoles as Novel Ppardelta Agonists. Part 2
Bioorg.Med.Chem.Lett., 16:5488-, 2006

PubMed Abstract: 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.

PubMed: 16931011
DOI: 10.1016/J.BMCL.2006.08.052

Experimental method

X-RAY DIFFRACTION (2.8 Å)