1KNU

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST

Summary for 1KNU

• Entry DOI: 10.2210/pdb1knu/pdb
• Related: 1PRG 2PRG
• Descriptor: PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA, (S)-3-(4-(2-CARBAZOL-9-YL-ETHOXY)-PHENYL)-2-ETHOXY-PROPIONIC ACID (3 entities in total)
• Functional Keywords: ppar, nuclear receptor, transcription, gene regulation, agonist complex, dna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 63046.26

Authors

Svensson, L.A.,Mortensen, S.B.,Fleckner, J.,Woeldike, H.F. (deposition date: 2001-12-19, release date: 2002-12-19, Last modification date: 2023-10-25)

Primary citation

Sauerberg, P.,Pettersson, I.,Jeppesen, L.,Bury, P.S.,Mogensen, J.P.,Wassermann, K.,Brand, C.L.,Sturis, J.,Woldike, H.F.,Fleckner, J.,Andersen, A.-S.T.,Mortensen, S.B.,Svensson, L.A.,Rasmussen, H.B.,Lehmann, S.V.,Polivka, Z.,Sindelar, K.,Panajotova, V.,Ynddal, L.,Wulff, E.M.
Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity
J.MED.CHEM., 45:789-804, 2002

PubMed Abstract: Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.

PubMed: 11831892
DOI: 10.1021/jm010964g

Experimental method

X-RAY DIFFRACTION (2.5 Å)