Abstract: The present invention provides a compound of formula (I): wherein R1-R5, R25, R26, Y, y, and X2 are as defined herein. The compounds activate human peroxisome proliferater activated receptors (hPPARs) and are useful for the treatment of associated disorders such as dyslipidemia, syndrome X, hypercholesteremia, type II diabetes mellitus, type I diabetes, insulin resistance, hyperlipidemia, and obesity.

Abstract: An isolated mineralocorticoid receptor (MR) polypeptide, or functional portion thereof, having one or more mutations that alter the solubility or crystal-forming properties and confer the ability to generate soluble protein complexes with the MR and ligands that only weakly bind the native polypeptide, and a polynucleotide encoding it are disclosed. Representative mutations are C808S and S810L substitutions. Expression of the MR polypeptide in E. coli is also provided. A solved three-dimensional crystal structure of an MR ligand binding domain polypeptide is also disclosed, along with a crystalline form of the MR ligand binding domain polypeptide.

Abstract: The present invention provides a compound of formula (I):

Abstract: A solved three-dimensional crystal structure of a glucocorticord receptor (GR) ? ligand binding domain polypeptide is disclosed, in the form of a crystalline glucocorticord receptor ? ligand binding domain polypeptide in complex with the ligand fluticasone propionate (FP) and a peptide derived from the co-activator TIF2. The GR/FP/TIF2 structure includes an expanded binding pocket not seen in other GR structures. Methods of designing steroid and non-steroid modulators of the biological activity of GR and other nuclear receptors (NRs) are also disclosed. In another aspect of the present invention homology models of androgen receptor (AR), progesterone receptor (PR) and mineralcorticoid receptor (MR) are disclosed, as well as methods of forming homology models for other NRs. Methods of forming a soluble GR/FP/TIF2 complex are also disclosed.

Abstract: The present invention provides a crystalline form of a substantially pure constitutive androstane receptor (CAR) polypeptide. Also provided is a crystalline form of a substantially pure constitutive androstane receptor (CAR) polypeptide in complex with a ligand. Also provided are methods for generating the crystalline forms of the present invention and methods for identifying and designing CAR ligands and modulators. Also provided are scalable three-dimensional configurations of points and computer readable storage media containing digitally encoded structural data.

Abstract: The present invention provides combinations of compounds of formula (I) and other therapeutic agents for the treatment of PPAR related diseases.

Abstract: A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, Wherein: R1 and R2 are independently hydrogen or C1-3 alkyl; X represents a bond, CH2 or O; R3 and R4 are independently hydrogen, C1-6 alkyl, OCH3, CF3, allyl or halogen; X1 is CH2, SO2, or CO; R5 is —C1-6 alkyl (optionally substituted by C1-6alkoxy or C1-6alkylthio), —C2-6 alkenyl, —C0-6 alkyl phenyl (wherein the phenyl is optionally substituted by one or more CF3, halogen, C1-3 alkyl, C1-3 alkoxy), —COC1-6 alkyl, SO2C1-6 alkyl; R6 is phenyl or a 6 membered heteroaryl group containing 1, 2 or 3 N atoms wherein the phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 moieties selected from the group consisting of C1-6 alkyl, halogen, —OC1-6 alkyl, —SO2C1-3 alkyl, phenyl (optionally substituted by one or more groups selected from halogen, CF3, C1-3 alkyl, OC1-3 alkyl, acetyl, CN).