Metabolon, Inc.

Plexxikon Inc.

Sirtris Pharmaceuticals, Inc.

Helmholtz Zentrum Munchen

Michael V Milburn

Kay A Lawton

Matthew W Mitchell

Danny Alexander

Walter Gall

Yun Fu Hu

Costel Chirila

Prabha N Ibrahim

Chao Zhang

Dean R Artis

Jack Lin

Weiru Wang

Heike I Krupka

Clarence R Hurt

James Arnold

John A Ryals

Lining Guo

Jeffery Edmond Cobb

Anne M Evans

Qibo Zhang

Klaus Peter Adam

Jacob Wulff

Luke Miller

Jean E Bemis

Chi B Vu

Jill C Milne

Joseph J Nunes

Roger Xie

Adam D Kennedy

Thomas J Jönsson

Ryan Douglas Michalek

Karl D Normington

Bryan Wittmann

Gabriele Kastenmueller

Jan Krumsiek

Karsten Suhre

Daniel P Stevens

Andrea Eckhart

Jeffery E Cobb

Jacob Edward Wulff

The present invention provides a method for diagnosing a disease or disorder selected from the group consisting of insulin resistance, a metabolic disorder, diabetes and pre-diabetes in a subject. The method comprises the step of determining the level of a compound represented by structural formula (VI): or a salt thereof. Compositions and method of making thereof are also described.

Diagnostic methods, therapeutic agents and uses thereof

The present invention provides a method for diagnosing a disease or disorder selected from the group consisting of insulin resistance, a metabolic disorder, diabetes and pre-diabetes in a subject. The method comprises the step of determining the level of a compound represented by structural formula (VI): or a salt thereof. Compositions and method of making thereof are also described. 

Methods are described herein for small molecule biochemical profiling of an individual subject for diagnosis of a disease or disorder, facilitating diagnosis of a disease or disorder, and/or identifying an increased risk of developing a disease or disorder in the individual subject. Aberrant levels of small molecules present in a sample from an individual subject are identified and diagnostic information relevant to the individual subject is obtained based on the identified aberrant levels. The obtained diagnostic information includes one or more of an identification of at least one biochemical pathway associated with the identified subset of the small molecules having aberrant levels, an identification at least one disease or disorder associated with the identified subset of the small molecules having aberrant levels, and an identification of at least one recommended follow up test associated with the identified subset of the small molecules having aberrant levels.

Small molecule biochemical profiling of individual subjects for disease diagnosis and health assessment

Biomarkers relating to cardiovascular disease, including atherosclerosis and cardiomyopathy, are provided, as well as methods for using such biomarkers as biomarkers for cardiovascular disease. In addition, methods for modulating the respective disorders or conditions of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for cardiovascular disease, including atherosclerosis and cardiomyopathy.

Biomarkers for cardiovascular diseases and methods using the same

Biomarkers relating to insulin resistance are provided, as well as methods for using the same as biomarkers for insulin resistance. Also provided are suites of small molecule entities as biomarkers for insulin resistance.

Biomarkers for insulin resistance and methods using the same

A method of elucidating the identity of an unknown metabolite comprising measuring amounts of known and unknown metabolites in subjects; associating the unknown metabolite with a specific gene from a gene association study; determining a protein associated with the specific gene and analyzing information for the protein; associating the unknown metabolite with concentrations and/or ratios of other metabolites in subjects; obtaining chemical structural data for the unknown metabolite; and using the information obtained to elucidate the identity of the unknown metabolite.

Identity elucidation of unknown metabolites

Methods for metabolomically determining the biological affects of compounds are described.

Methods of identifying biochemical pathways

Biomarkers relating to insulin resistance, pre-diabetes, type-2 diabetes, metabolic syndrome, atherosclerosis, and cardiomyopathy are provided, as well as methods for using such biomarkers as biomarkers for insulin resistance, pre-diabetes, type-2 diabetes, metabolic syndrome, atherosclerosis, and cardiomyopathy. In addition, methods for modulating the respective disorders or conditions of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for insulin resistance, pre-diabetes, type-2 diabetes, metabolic syndrome, atherosclerosis, and cardiomyopathy.

Biomarkers for impaired glucose tolerance and methods using the same

The present invention provides various biomarkers for hepatotoxicity and various methods of using the biomarkers Some of the biomarkers within the scope of this invention are cholate, glycochenodeoxycholate, glycocholate, taurine, 3-hyroxy-2-ethylpropionate, 4-imidazoleacetate, tyramine, anthranilate, 2'-deoxycytidine, N-acetyl aspartate (NAA), beta-hydroxy-hexanoate, and sarcosine (N-methylglycine) The methods of using the biomarkers include exposing a first hepatocyte culture to a test agent and comparing the levels of the one or more biomarkers obtained in the first hepatocyte culture to the levels of the one or more biomarkers obtained in a second hepatocyte culture without the test agent, where differential levels of the one or more biomarkers in the first hepatocyte culture as compared to the levels in the second hepatocyte culture is indicative of the test agent being a hepatotoxicant.

Determining liver toxicity of an agent using metabolite biomarkers

Biomarkers relating to insulin resistance are provided, as well as methods for using such biomarkers as biomarkers for insulin resistance. These biomarkers may be used to monitor the progression or regression of insulin resistance or to monitor the efficacy of insulin resistance treatment. Also provided are suites of small molecule entities as biomarkers for insulin resistance.

Biomarkers for monitoring insulin resistance and methods using the same

Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.

PPAR active compounds

Method for determining insulin sensitivity with biomarkers

Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, chemotherapeutic induced neuropathy, neuropathy associated with an ischemic event, polyglutamine diseases, ocular diseases and/or disorders, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Fused heterocyclic compounds and their use as sirtuin modulators

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Cary, NC, United States of America

Michael V Milburn