Abstract: Methods of and screens for detection of exogenous ligands in a biological sample without prior knowledge of the chemical structure of the ligand are disclosed. The novel screens and methods may be used to detect Illicit use of performance-enhancing steroids, which use has proliferated among a wide range of professional and amateur athletes. While these athletes were previously able to evade detection because the steroids were unknown to authorities, the present strategies can successfully detect such “designer steroids” without prior knowledge of their existence.

Abstract: Farnesyl pyrophosphate, the metabolically active form of farnesol, is a key precursor in the synthesis of cholesterol, carotenoids, steroid hormones, bile acids and other molecules involved in cellular growth and metabolism. A nuclear receptor has been identified that is transcriptionally activated by farnesol and related molecules. This novel signaling pathway can be modulated by the use of key metabolic intermediates (or analogs and/or derivatives thereof) as transcriptional regulatory signals.

Abstract: Estrogen-Related Receptor (ERR) modulating compounds and methods for synthesis of said compounds are described.

Abstract: Novel peroxisome proliferators-activated receptor subunits designated PPAR? and PPAR? are described. Nucleic acid sequences encoding the receptor subunits, expression vectors containing such sequences and host cells transformed with such vectors are also disclosed, as are heterodimeric PPAR receptors comprising at least one of the invention subunits, and methods for the expression of such novel receptors, and various uses therefor.

Abstract: Disclosed are novel compositions and novel methods for the creation of both the novel compounds and known compounds. Also disclosed are methods for use of the novel compounds for treating a variety of diseases relating to decreasing or preventing activation of estrogen receptors and/or estrogen related receptors.

Abstract: The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes. Reducing and/or preventing SXR activation therefore diminishes drug resistance and drug clearance and forms the basis of important therapeutic methods which increase the performance of drugs, such as taxanes. Screening and drug identification methods are described which can identify drugs which are not susceptible to SXR related inactivation and increased efflux. In addition, drugs which can reduce these effects for other agents are provided.

Abstract: The present invention relates to methods and compositions for modulating lipogenesis, lipid accumulation and lipid metabolism in a cell. These methods and compositions modulate genes which are controlled by LXR?, including the lipogenic transcription factor SREBP-1c.

Abstract: Methods for modulating the activity of the mammalian BAR/FXR receptor. The methods include methods of treating a hypocholesterolemic mammal comprising contacting the mammal with synthetic compounds able to modulate an activity characteristic of the BAR/FXR receptor. Other methods include a method of treating colon cancer in a mammal comprising administering a compound having a BAR/FXR antagonistic activity.

Abstract: The present invention provides methods for preventing or treating disorders associated with the degradation of cholesterol and bile alcohols through the use of ligands that interact with pregnane X receptors (PXR). In a preferred embodiment, PXR agonists are used to treat disorders associated with sterol 27-hydroxylase (CYP27) deficiency or mutation. The disorders associated with CYP27 deficiency include but not limited to cerebrotendinous xanthomatosis, cataracts, gallstone, tendon xanthomas, atherosclerosis, hepatomegaly, hypertriglyceridemia, and neurological and neuropsychiatric abnormalities such as peripheral neuropathy and dementia. In another preferred embodiment, PXR agonists are used to prevent or treat disorders that can be alleviated by enhancing the degradation of cholesterol or bile alcohols.

Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner.

Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner and screening for PPAR&ggr; ligands.

Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner.

Abstract: The orphan nuclear receptor SXR coordinately regulates drug clearance in response to a wide variety of xenobiotic compounds. The disclosure demonstrates that an HIV protease inhibitor binds SXR and activates its target genes. SXR ligands activate expression of MRP2, a critical regulator of bile flow and biliary drug excretion. Therefore, SXR binding compounds can be used for regulating drug clearance and treatment of hepatic disorders associated with impaired bile flow. The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes.

Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner and screening for PPAR&ggr; ligands.

Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner.