City of Hope

Donna Yu

Barry M Forman

James Lester Figarola

Donald David

Disclosed herein, inter alia, compounds and methods of use thereof for the modulation of bile acid receptor activity.

Bile acid receptor modulators and methods of use thereof

Provided herein are Famesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.

Farnesoid X receptor antagonists

Disclosed herein, inter alia, are compositions and methods useful for treating non-alcoholic fatty liver diseases.

ERR modulators and uses thereof

Provided herein, inter alia, are methods for the preparation of modulators of farnesoid X receptor (FXR), and compositions and uses of the modulators of FXR.

Bile acid derivatives and methods for synthesis and use

Provided herein are complexes of metformin or metformin analogues and a TGR5 ligand that are useful in treating diseases including diabetes, cardiovascular disease, and cancer.

TGR5 agonist complexes for treating diabetes and cancer

Provided herein are Farnesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.

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

Ligands for estrogen related receptors and methods for synthesis of said ligands

LXR nuclear receptor agonists have been previously shown to increase cholesterol efflux, raise plasma HDL cholesterol, stimulate cholesterol excretion, and reduce atherosclerotic lesions. However, these agonists have also been associated with the unwanted side effect of hypertriglyeridemia. This hypertriglyeridemia appears to be mediated by the LXR&#x3b1; subtype rather than LXR&#x3b2;, which suggests that LXR&#x3b2;-selective agonists are attractive candidates for modulation of human lipid metabolism. The present application provides novel LXR&#x3b2;-selective ligands that preferably modulate LXR&#x3b2; over LXR&#x3b1;. These ligands may be used to treat a variety of diseases associated with LXR, such as for example lipid metabolism disorders, atherosclerosis, Alzheimer disease, and inflammation.

Synthetic ligands selective for LXR&#x3b2; over LXR&#x3b1;, identification and methods of use thereof

A novel, improved method of synthesizing alkylated bile acid derivatives is provided. Such derivatives include, but are not limited to the active, potent, and selective FXR receptor agonist such as 6-ECDCA and other CA, DCA and CDCA derivatives. The first step of the synthesis selectively oxidates CDCA, CD, or DCA related starting material. An efficient combined deprotonation, trapping, ethylation, deprotection and reduction system is used to produce the desired alkylated bile acid derivatives. This practical synthesis offers a simple and economical pathway suitable for a large-scale manufacturing of alkylated bile acid derivatives including, but not limited to, 6-ECDCA.

Method of synthesizing alkylated bile acid derivatives

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.

Growing community of inventors

Arcadia, CA, United States of America

Donna Yu