Wen Xie, 57El Monte, CA

7413853, Aug 19, 2008

Jul 9, 2002

10/482555

Ronald M. Evans - La Jolla CA, US
Wen Xie - San Diego CA, US

The Salk Institute for Biological Studies - La Jolla CA

C12Q 1/68
C12Q 1/48
C12Q 1/34
G01N 33/53

435 6, 435 78, 435 15, 435 18

In accordance with the present invention, there are provided methods for modulating Phase II conjugating enzymes such as, for example, UGTs. Phase II conjugating enzymes such as UGTs function in concert with Phase I monooxygenase enzymes such as cytochrome P450 enzymes (CYPs) to eliminate steroids and xenobiotics. Nuclear receptors SXR/PXR and CAR are xenosensors regulating expression of CYP genes such as CYP3A and 2B. The ability of this group of receptors to regulate expression of UGT in response to steroids and/or xenobiotics provides novel approaches for direct regulation/activation of a glucuronidation pathway, thereby providing methods to achieve physiologic homeostasis with respect to steroids and/or xenobiotics. SXR/PXR and CAR regulation/activation of UGT represents the first evidence of receptors that can transduce/transactivate both Phase I and Phase II adaptive hepatic response. In another aspect, the present invention also provides transgenic rodents expressing one or more of SXR, CAR or PXR.

2008008, Apr 10, 2008

Aug 29, 2007

11/847163

Wen Xie - Pittsburgh PA, US
Haibiao Gong - Pittsburgh PA, US

University of Pittsburgh - Of the Commonwealth System of Higher Education - Pittsburgh PA

A61K 31/56
A61P 35/00

514182000

The invention provides a method of treating an estrogen responsive condition comprising administration of an agonist of an orphan nuclear receptor, wherein activation of the orphan nuclear receptor inhibits estrogen activity. The invention also provides a method of reducing the size of an estrogen responsive tumor comprising administration of an agonist of an orphan nuclear receptor, wherein activation of the orphan nuclear receptor inhibits estrogen activity. The invention also provides a pharmaceutical composition comprising an agonist of an orphan nuclear receptor and a pharmaceutically acceptable vehicle, wherein activation of the orphan nuclear receptor inhibits estrogen activity.

2012000, Jan 5, 2012

Nov 18, 2009

13/129711

Wen Xie - Pittsburgh PA, US
Jie Gao - Pittsburgh PA, US

UNIVERSITY OF PITTSBURGH-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION - Pittsburgh PA

A61K 36/282
A61K 31/515
A61K 31/37
A61P 3/10
A61K 31/429
A61K 31/7088
A61K 31/421
A61P 3/04
A61K 31/444
A61K 31/497

424740, 514335, 514270, 514457, 51425505, 514368, 514 44 R, 514374

The invention provides a method of controlling obesity or type two diabetes in a human. In accordance with the inventive method, the constitutive androstane receptor (CAR) is agonized within the human, which effectively controls obesity or type two diabetes.

6984773, Jan 10, 2006

Dec 9, 1999

09/458366

Ronald M. Evans - La Jolla CA, US
Bruce Blumberg - Irvine CA, US
Wen Xie - San Diego CA, US

The Salk Institute for Biological Studies - La Jolla CA

C12N 5/00
C12N 15/00
A01K 67/00
A01K 67/027

800 18, 800 8, 800 25, 435325

A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis. An assay is provided for identifying steroid drugs that are likely to cause drug interaction if administered to a subject in therapeutic amounts.